Comparative study on the efficacy of low-dose and full-dose BCG bladder perfusion therapy.

BACKGROUND: Full-dose BCG bladder perfusion therapy is effective, but there are serious side effects. Whether a low dose of BCG can reduce the side effects of treatment while maintaining its efficacy is still inconclusive. OBJECTIVE: To compare the efficacy of low-dose and full-dose BCG bladder perfusion therapy and to provide reference for individual treatment of bladder cancer. METHODS: All relevant literature published in PubMed, Web of Science, and Embrase databases up to April 2024 was searched. The results and shortcomings of the existing literature are analyzed, the cognitive gaps between different studies are pointed out, and suggestions are made for future research. RESULTS: A total of 32 pieces of literature were included. Twelve studies found that the efficacy of full-dose BCG perfusion was significantly better than that of low-dose BCG perfusion, and 20 studies found no statistical difference between low-dose and full-dose BCG perfusion CONCLUSION: Although there is no significant difference in the efficacy of full-dose and low-dose BCG in bladder perfusion, the trend indicates that the efficacy of full-dose BCG is still the most accurate. In cases where BCG resources are scarce or patients are intolerant, low-dose BCG bladder perfusion therapy may be an alternative to full-dose BCG bladder perfusion therapy. High-quality, large-sample prospective cohort studies (or randomized controlled studies) are still needed in the future.

Impact of laparoscopic training course for surgical trainees based on an evidence-based pedagogical framework: randomized trial.

BACKGROUND: The 'Learn, See, Practice, Prove, Do, Maintain' (LSPPDM) pedagogical framework is an evidence-based framework developed through a careful review and synthesis of the literature. The purpose of the study was to explore the effectiveness and applicability of the LSPPDM pedagogical framework in the laparoscopic training course for surgical residents. METHODS: Prospective study of surgical residents who underwent standardized surgical residency training in a single institution from December 2020 to December 2022. Trainees were randomized to either the pedagogical group (6-step LSPPDM pedagogical framework) or traditional group (2-step traditional approach with twice-weekly lectures and a weekly laparoscopic operating skills session). The Global Operative Assessment of Laparoscopic Skills scale was used for technical skills, and the Non-Technical Skills for Surgeons assessment form was used for non-technical skills. RESULTS: Sixty trainees were randomized. The pedagogical group scored higher on subjective perception (P < 0.050) and the theoretical assessment (mean(s.d.) 41.83(6.66)) than those in the traditional group (37.83(5.77)) (P = 0.016). Trainees in the pedagogical group took less time to complete the assessment of models, had fewer failures and higher scores, took less time to complete laparoscopic sutures and knots, showed better proficiency with laparoscopic instruments, and completed at higher quality (P < 0.050). Trainees performing laparoscopic cholecystectomy in animal models demonstrated higher technical and non-technical skill scores in the pedagogical group (P < 0.050). 'Tissue handling' and 'Decision making' were common areas for improvement for both groups of trainees. CONCLUSIONS: The LSPPDM pedagogical framework is feasible and demonstrated improvements in technical and non-technical skills in surgical trainees compared to a traditional training programme.

Effect of smoking on the recurrence and progression of non-muscle-invasive bladder cancer.

BACKGROUND: It is well established that smoking is the most significant risk factor for bladder cancer, yet the impact of smoking on the recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) remains a contentious issue. OBJECTIVE: To review all relevant literature published to date, providing a comprehensive assessment of the effects of smoking on the recurrence and progression of NMIBC, thereby offering a basis for smoking cessation management in NMIBC patients. METHODS: A search was conducted for all relevant literature published up to April 2024 in PubMed, Web of Science, and Embase databases. The existing literature results and deficiencies were analyzed, and the gaps in understanding between different studies were highlighted, with recommendations for future research. RESULTS: A total of 24 studies were included in this work. Among them, 14 studies suggested that smoking promotes the recurrence and progression of NMIBC, while another 10 studies concluded that smoking has no effect on the recurrence and progression of NMIBC patients. CONCLUSIONS: Our research indicates that smoking increases the risk of recurrence and progression in NMIBC patients, and quitting smoking can improve health-related quality of life. High-quality, large-sample prospective cohort studies (or randomized controlled studies) are still needed in the future.

Systematic Druggable Genome-Wide Mendelian Randomization Identifies Therapeutic Targets for Functional Outcome After Ischemic Stroke.

BACKGROUND: Stroke is a leading cause of death worldwide, with a lack of effective treatments for improving the prognosis. The aim of the present study was to identify novel therapeutic targets for functional outcome after ischemic stroke . METHODS AND RESULTS: Cis-expression quantitative trait loci data for druggable genes were used as instrumental variables. The primary outcome was the modified Rankin Scale score at 3 months after ischemic stroke, evaluated as a dichotomous variable (3-6 versus 0-2) and also as an ordinal variable. Drug target Mendelian randomization, Steiger filtering analysis, and colocalization analysis were performed. Additionally, phenome-wide Mendelian randomization analysis was performed to identify the safety of the drug target genes at the genetic level. Among >2600 druggable genes, genetically predicted expression of 16 genes (ABCC2, ATRAID, BLK, CD93, CHST13, NR1H3, NRBP1, PI3, RIPK4, SEMG1, SLC22A4, SLC22A5, SLCO3A1, TEK, TLR4, and WNT10B) demonstrated the causal associations with ordinal modified Rankin Scale (P<1.892×10-5) or poor functional outcome (modified Rankin Scale 3-6 versus 0-2, P<1.893×10-5). Steiger filtering analysis suggested potential directional stability (P<0.05). Colocalization analysis provided further support for the associations between genetically predicted expression of ABCC2, NRBP1, PI3, and SEMG1 with functional outcome after ischemic stroke. Furthermore, phenome-wide Mendelian randomization revealed additional beneficial indications and few potential safety concerns of therapeutics targeting ABCC2, NRBP1, PI3, and SEMG1, but the robustness of these results was limited by low power. CONCLUSIONS: The present study revealed 4 candidate therapeutic targets for improving functional outcome after ischemic stroke, while the underlying mechanisms need further investigation.

Enhancing Standardized Practices for Oral Mucositis Prevention in Pediatric Hematopoietic Stem Cell Transplantation: A Best Practice Implementation Project.

Background: Oral mucositis (OM) poses a significant challenge in children undergoing hematopoietic stem cell transplantation (HSCT). There is a gap between clinical practice and the evidence, and nursing practices is not standardized. Objective: This study aims to evaluate the effectiveness of applying the evidence for preventing HSCT chemotherapy-induced OM in children and to elevate the nurses' compliance to the evidence. Methods: Following the clinical evidence practice application model of the Joanna Briggs Institute (JBI) evidence-Based Care Center. The process included reviewing literature, extracting evidence, identifying gaps, developing audit criteria, conducting a baseline audit, creating an action plan, implementing evidence-based interventions, and assessing outcomes. Results: After the evidence implementation, 6 out of 12 audit criteria with poor compliance are significantly improved, with statistically significant differences (P<0.05). The incidence of OM decreases, with a statistically significant difference (66.6% vs 36.7%, P=0.02). The incidence of grade I, II, III, and IV OM also decreases (30% vs 23.3%, 23.3% vs 13.4%, 10% vs 0%, and 3.3% vs 0%). Ultimately, the standardized oral care practice routine and workflows to prevent OM were established. Conclusion: Bridging the gap between evidence and clinical practice can standardize nurse behavior, decrease the incidence of OM, and lower the OM severity in children undergoing HSCT.

Bruton's tyrosine kinase inhibition ameliorated neuroinflammation during chronic white matter ischemia.

Chronic cerebral hypoperfusion (CCH), a disease afflicting numerous individuals worldwide, is a primary cause of cognitive deficits, the pathogenesis of which remains poorly understood. Bruton's tyrosine kinase inhibition (BTKi) is considered a promising strategy to regulate inflammatory responses within the brain, a crucial process that is assumed to drive ischemic demyelination progression. However, the potential role of BTKi in CCH has not been investigated so far. In the present study, we elucidated potential therapeutic roles of BTK in both in vitro hypoxia and in vivo ischemic demyelination model. We found that cerebral hypoperfusion induced white matter injury, cognitive impairments, microglial BTK activation, along with a series of microglia responses associated with inflammation, oxidative stress, mitochondrial dysfunction, and ferroptosis. Tolebrutinib treatment suppressed both the activation of microglia and microglial BTK expression. Meanwhile, microglia-related inflammation and ferroptosis processes were attenuated evidently, contributing to lower levels of disease severity. Taken together, BTKi ameliorated white matter injury and cognitive impairments induced by CCH, possibly via skewing microglia polarization towards anti-inflammatory and homeostatic phenotypes, as well as decreasing microglial oxidative stress damage and ferroptosis, which exhibits promising therapeutic potential in chronic cerebral hypoperfusion-induced demyelination.

Decomposition and scenario analysis of agricultural carbon emissions in Heilongjiang, China.

Background: As a key agricultural region in China, Heilongjiang Province has experienced significant carbon emissions over the past few decades. To understand the underlying factors and future trends in these emissions, a comprehensive analysis was conducted from 1993 to 2030. Methods: The agricultural carbon emissions from 1993 to 2020 were estimated using the emission factor method. To analyze the influencing factors and future trends of these emissions, the study employed the Logarithmic Mean Divisia Index (LMDI) and integrated it with the Stochastic Impacts by Regression on Population, Affluence, and Technology (STIRPAT) model. Results: Results showed that (1) the agricultural carbon emissions in Heilongjiang were primarily driven by rice cultivation, followed by fertilizer production and irrigation electricity. (2) The economic and labor structure effects were the main driving factors of agricultural carbon emissions, while the population, demographic, and intensity effects were the main inhibitors. (3) Agricultural carbon emissions in Heilongjiang Province peaked in 2016 with 69.6 Mt CO2-eq and could subsequently decline by -3.92% to -4.52% between 2020 and 2030 in different scenario simulations. In the future, Heilongjiang Province should prioritize the reduction of agricultural carbon emissions from rice production. Adjusting the planting structure, managing the layout of rice paddies, and promoting the cultivation of dry rice varieties would significantly contribute to mitigating agricultural carbon emissions.

PA-MSHA improves prognosis of patients undergoing radical cystectomy: a retrospective cohort study using inverse probability of treatment weighting.

Objective: To observe the effect of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on the prognosis and the incidence of lymphatic leakage in patients undergoing radical cystectomy (RC). Method: A total of 129 patients who underwent RC in Lanzhou University Second Hospital from 2013 to 2022 were enrolled in this study. They were divided into 43 patients treated with PA-MSHA and 86 patients in the control group. Inverse probability of treatment weighting (IPTW) was applied to reduce potential selection bias. Kaplan-Meier method and Cox regression analysis were used to analyze the effect of PA-MSHA on the survival of patients and the incidence of postoperative lymphatic leakage. Results: The PA-MSHA group exhibited improved overall survival (OS) and cancer-specific survival (CSS) rates compared to the control group. The 3-year and 5-year overall survival (OS) rates for the PA-MSHA group were 69.1% and 53.2%, respectively, compared to 55.6% and 45.3% for the control group (Log-rank=3.218, P=0.072). The 3-year and 5-year cancer-specific survival (CSS) rates for the PA-MSHA group were 73.3% and 56.5%, respectively, compared to 58.0% and 47.3% for the control group (Log-rank=3.218, P=0.072). Additionally, the 3-year and 5-year progression-free survival (PFS) rates for the PA-MSHA group were 74.4% and 56.8%, respectively, compared to 57.1% and 52.2% for the control group (Log-rank=2.016, P=0.156). Multivariate Cox regression analysis indicates that lymph node metastasis and distant metastasis are poor prognostic factors for patients, while the use of PA-MSHA can improve patients' OS (HR: 0.547, 95%CI: 0.304-0.983, P=0.044), PFS (HR: 0.469, 95%CI: 0.229-0.959, P=0.038) and CSS (HR: 0.484, 95%CI: 0.257-0.908, P=0.024). The same trend was observed in the cohort After IPTW adjustment. Although there was no significant difference in the incidence of postoperative lymphatic leakage [18.6% (8/35) vs. 15.1% (84.9%), P=0.613] and pelvic drainage volume [470 (440) ml vs. 462.5 (430) ml, P=0.814] between PA-MSHA group and control group, PA-MSHA could shorten the median retention time of drainage tube (7.0 d vs 9.0 d) (P=0.021). Conclusion: PA-MSHA may improve radical cystectomy in patients with OS, PFS, and CSS, shorten the pelvic drainage tube retention time.

Nutritional and Body Composition Changes in Paediatric ß-Thalassemia Patients Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Study Using Bioelectrical Impedance Analysis.

Objective: This retrospective study evaluated nutritional status and body composition changes in paediatric ß-thalassemia (ß-TM) patients before and after hematopoietic stem cell transplantation (HSCT), using bioelectrical impedance analysis (BIA), and explored their relationship with HSCT outcomes. Methods: A cohort of 40 paediatric ß-TM patients undergoing allogeneic HSCT was assessed for their nutritional status, anthropometric parameters, including body mass index (BMI), weight, and height, and body composition parameters pre-and post-HSCT, focusing on BIA measurements, including intracellular water (ICW), extracellular water (ECW), fat mass (FAT), fat-free mass (FFM), Skeletal Muscle Mass (SMM), soft Lean Mass (SLM), percent body fat (PBF), Body Cell Mass (BCM), Phase angle (PA) and muscle balance pre- and post-HSCT. Post-HSCT clinical outcomes, including acute graft-vs-host disease (aGVHD), engraftment time, oral mucositis (OM), sinusoidal obstruction syndrome (SOS), and diarrhoea in relation to nutrition status after HSCT were analysed. Results: After HSCT, 28.21% experienced diminished nutritional status, with 71.43% of those who were wasting before HSCT showing diminished nutritional status, significantly higher than the normal group (18.75%, P = 0.012). Anthropometric changes included significant weight reduction (87.5%, 22.15 ± 7.46 vs 20.74 ± 6.57, P < 0.001) and BMI decrease (90%, 15.19 ± 1.70 vs 14.05 ± 1.48, P < 0.001). Body composition parameters, which are FFM, SMM, SLM, ICW, ECW, BCM, and PA (18.26 ± 5.71 vs 17.27 ± 5.19, 8.68 ± 3.30 vs 7.93 ± 3.02, 17.11 ± 5.28 vs 16.06 ± 4.84, 8.19 ± 2.54 vs 7.62 ± 2.31, 5.15 ± 1.58 vs 4.94 ± 1.47, 11.74 ± 3.63 vs 10.92 ± 3.32, 4.42 ± 0.50 vs 3.90 ± 0.57, respectively, P < 0.001) analysis revealed significant decreases. No significant differences in clinical outcomes were observed based on nutritional status. Conclusion: Paediatric ß-TM patients undergoing HSCT exhibit significant changes in nutrition status and body composition, emphasizing the need for focused attention on malnourished children who are more prone to diminished nutritional status. Comprehensive BIA aids in understanding the impact, urging consideration for extended follow-up and larger cohorts in future research.

Improved antioxidative and antibacterial activity of epigallocatechin gallate derivative complexed by zinc cations and chitosan.

Epigallocatechin gallate (EGCG) has attracted increasing attention thanks to its multi-bioactivities, and people are keen on improving the antioxidative and antibacterial performance of EGCG. Based on the favorable biofunctionality of Zn2+ and chitosan (CS), an EGCG derivative with a novel formula, i.e., EGCG-Zn-CS, is presented in this study. The structure of EGCG-Zn-CS was characterized by FT-IR, UV-vis, TGA, XPS, and SEM-EDS. The radical elimination results indicate that 0.1 mg mL-1 of EGCG-Zn-CS demonstrates DPPH radical and hydroxyl radical scavenging activities of 94.8% and 92.3%, while 0.1 mg mL-1 of EGCG exhibits only 78.5% and 75.6%, respectively, which means improved antioxidative activity of EGCG-Zn-CS was obtained. Inhibitory experiments against Staphylococcus aureus and Escherichia coli reveal that the minimal inhibitory concentrations (MICs) of EGCG-Zn-CS were 15.625 µg mL-1 and 187.5 µg mL-1, whereas the minimal bactericide concentrations (MBCs) were 46.875 µg mL-1 and 750 µg mL-1, respectively, which indicate that EGCG-Zn-CS exerts much higher antibacterial activity than EGCG. It can be concluded that the complexing of zinc cations and CS could amazingly improve both the antioxidative and antibacterial activity of EGCG, and it is expected that an exploration of EGCG-Zn-CS may inspire the development of simultaneous effective antioxidant and antibacterial agents.

Gene expression prognostic of early relapse risk in low-risk B-cell acute lymphoblastic leukaemia in children.

ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low-risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low-risk ETV6::RUNX1-positive B-cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome-wide transcriptome and single-nucleotide variants. We found high TIMD4 expression (> 85th-percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low-risk ETV6::RUNX1-positive B-cell ALL (N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] (p = 0.04) for early relapse. In another validation cohort including 78 children with low-risk ETV6::RUNX1-negative B-cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low-risk B-cell ALL in children might be associated with high risk for early relapse.

Towards better laparoscopic video segmentation: A class-wise contrastive learning approach with multi-scale feature extraction.

The task of segmentation is integral to computer-aided surgery systems. Given the privacy concerns associated with medical data, collecting a large amount of annotated data for training is challenging. Unsupervised learning techniques, such as contrastive learning, have shown powerful capabilities in learning image-level representations from unlabelled data. This study leverages classification labels to enhance the accuracy of the segmentation model trained on limited annotated data. The method uses a multi-scale projection head to extract image features at various scales. The partitioning method for positive sample pairs is then improved to perform contrastive learning on the extracted features at each scale to effectively represent the differences between positive and negative samples in contrastive learning. Furthermore, the model is trained simultaneously with both segmentation labels and classification labels. This enables the model to extract features more effectively from each segmentation target class and further accelerates the convergence speed. The method was validated using the publicly available CholecSeg8k dataset for comprehensive abdominal cavity surgical segmentation. Compared to select existing methods, the proposed approach significantly enhances segmentation performance, even with a small labelled subset (1-10%) of the dataset, showcasing a superior intersection over union (IoU) score.

The mechanistic interaction, aggregation and neurotoxicity of α-synuclein after interaction with glycyrrhizic acid: Modulation of synucleinopathies.

This article reveals the binding mechanism between glycyrrhizic acid (GA) and α-synuclein to may provide further information for the modulation of synucleinopathies using bioactive compounds. Therefore, the inhibitory activities of GA against α-synuclein aggregation and induced neurotoxicity were evaluated using different assays. Results showed that α-synuclein-GA binding was mediated by intermolecular hydrogen bonds leading to the formation of a slightly folded complex. Theoretical studies revealed that GA binds to the N-terminal domain of α-synuclein and triggers a compact structure around a major part of the N-terminal and the NAC regions along with fluctuations in the C-terminal domain, which are prerequisites for the inhibition of α-synuclein aggregation. Then, the cellular assays showed that GA as a potential small molecule can inhibit the oligomerization of α-synuclein and relevant neurotoxicity through modulation of neural viability, membrane leakage, and ROS formation in a concentration-dependent manner. As a result, the primary mechanism of GA's anti-aggregation and neuroprotective activities is the reorganized α-synuclein structure and fluctuating C-terminal domain, which promotes long-range transient intramolecular contacts between the N-terminal and the C-terminal domain.

Dawn of CAR-T cell therapy in autoimmune diseases.

ABSTRACT: Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo , CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

Risk factors of high fluid absorption in patients treated with mini-PCNL: a single-center prospective study.

BACKGROUND: The factors influencing fluid absorption in mini-percutaneous nephrolithotripsy (mini-PCNL) are still unknown. We aim to investigate the factors that influence irrigation fluid absorption during mini-PCNL. METHODS: A total of 94 patients who underwent mini-PCNL were included in this prospective study. The endoscopic surgical monitoring system (ESMS) was used to measure the volume of irrigation fluid absorbed during the procedure. Irrigating time, the total volume of irrigation fluid, stone size, S.T.O.N.E. score, hemoglobin, electrolyte levels, and postoperative complications were recorded. RESULTS: A significant correlation was observed between fluid absorption and the presence of postoperative fever, and based on this phenomenon, patients were divided into low and high fluid absorption groups. The serum creatinine level in the high fluid absorption group was significantly high (7 vs. 16.5, p = 0.02). Significant differences were observed between the low and high fluid absorption groups in terms of mean stone size (21.70 mm vs. 26.78 mm), presence of stone burden ≥ 800 mm2 (4% vs. 23%), S.T.O.N.E. score > 8 (4% vs. 38%), the fluid used > 18,596 ml (19% vs. 78%), irrigation time (55.61 min vs. 91.28 min), and perfusion rate (24% vs. 45%) (all p < 0.05). The rates of postoperative fever and SIRS in the high fluid absorption group were significantly high (p < 0.05). CONCLUSIONS: Mean stone size, presence of stone burden ≥ 800 mm2, S.T.O.N.E. score > 8, the fluid used > 18596 mL, irrigation time, and perfusion rate are risk factors of intraoperative fluid absorption in mini-PCNL.

Causal association between the peripheral immunity and the risk and disease severity of multiple sclerosis.

Background: Growing evidence links immunological responses to Multiple sclerosis (MS), but specific immune factors are still unclear. Methods: Mendelian randomization (MR) was performed to investigate the association between peripheral hematological traits, MS risk, and its severity. Then, further subgroup analysis of immune counts and circulating cytokines and growth factors were performed. Results: MR revealed higher white blood cell count (OR [95%CI] = 1.26 [1.10,1.44], P = 1.12E-03, P adjust = 3.35E-03) and lymphocyte count (OR [95%CI] = 1.31 [1.15,1.50], P = 5.37E-05, P adjust = 3.22E-04) increased the risk of MS. In further analysis, higher T cell absolute count (OR [95%CI] = 2.04 [1.36,3.08], P = 6.37E-04, P adjust = 2.19E-02) and CD4+ T cell absolute count (OR [95%CI] = 2.11 [1.37,3.24], P = 6.37E-04, P adjust = 2.19E-02), could increase MS risk. While increasing CD25++CD4+ T cell absolute count (OR [95%CI] = 0.75 [0.66,0.86], P = 2.12E-05, P adjust = 1.72E-03), CD25++CD4+ T cell in T cell (OR [95%CI] = 0.79[0.70,0.89], P = 8.54E-05, P adjust = 5.29E-03), CD25++CD4+ T cell in CD4+ T cell (OR [95%CI] = 0.80[0.72,0.89], P = 1.85E-05, P adjust = 1.72E-03), and CD25++CD8+ T cell in T cell (OR [95%CI] = 0.68[0.57,0.81], P = 2.22E-05, P adjust = 1.72E-03), were proved to be causally defensive for MS. For the disease severity, the suggestive association between some traits related to CD4+ T cell, Tregs and MS severity were demonstrated. Moreover, elevated levels of IL-2Ra had a detrimental effect on the risk of MS (OR [95%CI] = 1.22 [1.12,1.32], P = 3.20E-06, P adjust = 1.34E-04). Conclusions: This study demonstrated a genetically predicted causal relationship between elevated peripheral immune cell counts and MS. Subgroup analysis revealed a specific contribution of peripheral immune cells, holding potential for further investigations into the underlying mechanisms of MS and its severity.

Association of dietary carotenoid intake with the prevalence kidney stones among the general adult population.

PURPOSE: This study was to examine whether higher dietary carotenoid intake levels were associated with a lower prevalence of kidney stones. MATERIALS AND METHODS: This study analyzed data from 2007 to 2018 National Health and Nutrition Examination Survey (NHANES) project. Dietary carotenoid intake (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein/zeaxanthin) was assessed using two 24-h dietary recall interviews. Multiple logistic regression and weighted quantile sum (WQS) regression were applied to examine the associations between five dietary carotenoids alone, compounds, and the prevalence of kidney stones. The dose-response relationships were analyzed by restricted cubic spline regression. RESULTS: A total of 30,444 adults (2909 participants with kidney stones) were included in the analysis. The mean age of the participants was 49.95 years and 49.2% of the participants were male. Compared with the first quartile, the fourth quartile of α-carotene (odds ratio [OR] = 0.82 [0.73-0.92]), ß-carotene (OR = 0.79 [0.70-0.89]), ß-cryptoxanthin (OR = 0.88 [0.79-0.99]), and lutein/zeaxanthin (OR = 0.80 [0.71-0.91]) were significantly and inversely associated with the prevalence of kidney stones after adjusting for confounders. The dose-response analysis showed a linear relationship between five dietary carotenoid intake levels and the prevalence of kidney stones. Further WQS analysis revealed that the combination of all five dietary carotenoids was negatively associated with and the prevalence of kidney stones, with the largest effect coming from ß-carotene (weight = 0.538). CONCLUSION: Our findings indicated that higher dietary carotenoid intake levels were associated with decreased prevalence of kidney stones, and increasing the intake of foods rich in ß-carotene may prevent the development of kidney stones.

Outcome of first or second transplantation using unrelated umbilical cord blood without ATG conditioning regimen for pediatric bone marrow failure disorders.

BACKGROUND: Unrelated umbilical cord blood transplantation (UCBT) for bone marrow failure (BMF) disorders using conditioning regimens without Anti-Thymocyte Globulin (ATG) has been used as an alternative transplantation for emerging patients without matched-sibling donors. Experience with this transplant modality in children is limited, especially as a secondary treatment for transplant failure patients. PROCEDURE: We retrospectively reviewed 17 consecutive bone marrow failure patients who underwent unrelated umbilical cord blood transplantation in our center and received conditioning regimens of Total Body Irradiation (TBI) or Busulfan (BU) + Fludarabine (FLU) + Cyclophosphamide (CY). RESULTS: Among the 17 BMF patients, 15 patients were treated with first cord blood transplantation and another 2 with secondary cord blood transplantation because of graft failure after first haploidentical stem cell transplantation at days +38 and +82. All patients engrafted with a median donor cell chimerism of 50 % at days +7 (range, 16 %-99.95 %) and finally rose to 100 % at days +30. Median time to neutrophil engraftment was 19 days (range, 12-30) and time to platelet engraftment was 32 days (range, 18-61). Pre-engraftment syndrome (PES) was found in 16 patients (94.11 %, 16/17). Cumulative incidence of grades II to IV acute GVHD was 58.8 % (95 % CI: 32.7-84.9 %), and 17.6 % (95 % CI: 2.6-37.9 %) of patients developed chronic GVHD. The 3-year overall survival (OS) and failure-free survival (FFS) rates were 92.86 ± 6.88 %. CONCLUSION: UCBT is an effective alternative treatment for bone marrow failure pediatric patients. TBI/BU + FLU + CY regimen ensure a high engraftment rate for unrelated umbilical cord blood transplantation, which overcomes the difficulty of graft failure. Secondary salvage use of cord blood transplantation may still be useful for patients who have failed after other transplantation.

Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion.

BACKGROUND: Impaired glucose tolerance (IGT) is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes. When IGT occurs, insulin sensitivity decreases, causing a reduction in insulin secretion and an increase in glucagon secretion. Recently, vascular endothelial growth factor B (VEGFB) has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity. Therefore, we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion, thus contributing to the prevention and cure of prediabetes. AIM: To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT. METHODS: We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression. Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay, and the protein expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) was determined using western blot. Further, mRNA expression of forkhead box protein O1, phosphoenolpyruvate carboxykinase, and glucose-6 phosphatase was detected via quantitative polymerase chain reaction, and the correlation between the expression of proteins was analyzed via bioinformatics. RESULTS: In mice with IGT and VEGFB knockout, glucagon secretion increased, and the protein expression of PI3K/AKT decreased dramatically. Further, in mice with VEGFB overexpression, glucagon levels declined, with the activation of the PI3K/AKT signaling pathway. CONCLUSION: VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.

IN VITRO EVALUATION OF A NOVEL AUTOMATIC INTRAOPERATIVE BLOOD LOSS MONITOR.

INTRODUCTION: Accurate and real-time monitoring of surgical blood loss is essential for ensuring intraoperative safety. However, there is currently no standard way to assess the amount of blood lost in patients during surgery. This study aims to evaluate the accuracy and precision of a new automatic intraoperative blood loss monitor, which can measure both free blood volume and blood content in sponges in real time. METHODS: The monitor uses an integrated photoelectric probe to gauge hemoglobin levels in both free blood and blood taken from surgical sponges. This data, combined with initial hemoglobin levels, is processed using specific calculations to determine blood volume. We created 127 diverse free blood samples and 160 blood-containing sponge samples by utilizing fresh pig blood and physiological saline. The monitor then measured these samples. We subsequently compared its measurements with actual values acquired through physical measurements, detecting both agreement and measurement errors. Repeated measurements were performed to calculate the coefficient of variation, thereby evaluating the monitor's precision. RESULTS: The estimated blood loss percentage error of the monitor was 5.2% for free blood, -5.7% for small sponge, -6.3% for medium sponge, and -6.6% for large sponge. The coefficient of variation of free blood with different hemoglobin concentrations measured by the monitor was less than 10%. Bland-Altman analysis showed that the limits of agreement between the monitor and the reference method were all within the acceptable clinical range. CONCLUSION: The new automatic intraoperative blood loss monitor is an accurate and reliable device for monitoring both free blood and surgical sponge blood, and shows high performance under various clinical simulation conditions.