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1.
JMIR Med Inform ; 12: e56893, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38968600

ABSTRACT

BACKGROUND: To circumvent regulatory barriers that limit medical data exchange due to personal information security concerns, we use homomorphic encryption (HE) technology, enabling computation on encrypted data and enhancing privacy. OBJECTIVE: This study explores whether using HE to integrate encrypted multi-institutional data enhances predictive power in research, focusing on the integration feasibility across institutions and determining the optimal size of hospital data sets for improved prediction models. METHODS: We used data from 341,007 individuals aged 18 years and older who underwent noncardiac surgeries across 3 medical institutions. The study focused on predicting in-hospital mortality within 30 days postoperatively, using secure logistic regression based on HE as the prediction model. We compared the predictive performance of this model using plaintext data from a single institution against a model using encrypted data from multiple institutions. RESULTS: The predictive model using encrypted data from all 3 institutions exhibited the best performance based on area under the receiver operating characteristic curve (0.941); the model combining Asan Medical Center (AMC) and Seoul National University Hospital (SNUH) data exhibited the best predictive performance based on area under the precision-recall curve (0.132). Both Ewha Womans University Medical Center and SNUH demonstrated improvement in predictive power for their own institutions upon their respective data's addition to the AMC data. CONCLUSIONS: Prediction models using multi-institutional data sets processed with HE outperformed those using single-institution data sets, especially when our model adaptation approach was applied, which was further validated on a smaller host hospital with a limited data set.

2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 384-392, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38953262

ABSTRACT

Primary liver cancer is one of the most common malignant tumors of the digestive system,of which hepatocellular carcinoma (HCC) accounts for more than 90% of the total cases.The patients with early HCC treated by surgical resection generally demonstrate good prognosis.However,due to the insidious onset,HCC in the vast majority of patients has progressed to the mid-to-late stage when being diagnosed.As a result,surgical treatment has unsatisfactory effects,and non-surgical treatment methods generally have severe side effects and low tumor selectivity.Nanoparticles (NP) with small sizes,large specific surface areas,and unique physical and chemical properties have become potential carriers for the delivery of therapeutic agents such as drugs,genes,and cytokines.The nano-delivery systems with NP as the carrier can regulate the metabolism and transformation of drugs,genes,and cytokines in vivo from time,space,and dose via functional modification,showing great potential in the treatment of HCC.This paper introduces the current status and advantages of several common nano-delivery systems,including organic nano-carriers,inorganic nano-carriers,and exosomes,in the treatment of HCC.Furthermore,this paper summarizes the mechanisms of NP-based nano-carriers in treating HCC and provides reference for the development of new nano-delivery systems.


Subject(s)
Carcinoma, Hepatocellular , Drug Delivery Systems , Liver Neoplasms , Nanoparticles , Nanotechnology , Carcinoma, Hepatocellular/drug therapy , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/therapy , Nanoparticles/chemistry , Nanotechnology/methods , Drug Carriers
3.
Antonie Van Leeuwenhoek ; 117(1): 98, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981868

ABSTRACT

An aerobic, Gram-stain-negative bacterium, designated as SYSU D00382T, was sourced from soil of Gurbantunggut Desert, PR China. The strain was short-rod-shaped, oxidase-positive and catalase-negative, with yellow-colored, convex, round, and smooth colonies on TSA plate. Growth and proliferation occurred at 4-37 °C (optimal: 28-30 °C), pH 5.0-8.0 (optimal: pH 6.0-7.0) and NaCl concentration of 0-2.5% (optimal: 0-0.5%). The 16S rRNA gene based phylogenetic assessment showed that SYSU D00382T belonged to the genus Pedobacter, and was most closely related to Pedobacter ginsengisoli Gsoil 104T with similarity of 97.7%. The genomic DNA G+C content of SYSU D00382T was 46.4%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between SYSU D00382T and P. ginsengisoli Gsoil 104T were 75.7% and 17.5%, respectively. The main polar lipid was phosphatidylethanolamine. The major fatty acids (> 5%) were iso-C15:0, iso-C17:0 3-OH, summed features 3 and 9. The sole respiratory quinone identified was MK-7. The phylogeny based on 16S rRNA gene and whole-genome sequences revealed that SYSU D00382T formed a robust lineage with P. ginsengisoli Gsoil 104T. Based on phenotypic, phylogenetic and genotypic data, a novel specie named Pedobacter deserti sp. nov. is proposed. The type strain is SYSU D00382T (= CGMCC 1.18627T = MCCC 1K04972T = KCTC 82279T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Desert Climate , Fatty Acids , Pedobacter , Phylogeny , RNA, Ribosomal, 16S , Soil Microbiology , Pedobacter/genetics , Pedobacter/classification , Pedobacter/isolation & purification , Pedobacter/physiology , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Fatty Acids/analysis , China , Nucleic Acid Hybridization , Sequence Analysis, DNA
4.
Angew Chem Int Ed Engl ; : e202405868, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977413

ABSTRACT

Consequences of intramolecular ionic interactions in determining the reactivity of functional groups are of interest because they provide insights into how nature deploys seemingly reactive functionalities to be rather ubiquitous. Of specific interest are the quaternary ammonium ions in lipids. In this work, we investigate the effect of intramolecular electrostatic interactions in zwitterionic functionalities by judiciously incorporating them as leaving groups at the α-position of an α,ß-unsaturated ester-based lipid headgroup. We find that electrostatic stabilization indeed plays a critical role in both the reaction kinetics with nucleophiles and the thermodynamics of lipid formation. We further leverage these findings to fabricate both triggerable assembly and disassembly of liposomal supramolecular assemblies in the presence of nucleophiles.

5.
World J Gastrointest Oncol ; 16(6): 2520-2530, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38994151

ABSTRACT

BACKGROUND: Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide. Neoadjuvant chemoradiotherapy (nCRT) is standard for locally advanced rectal cancer (LARC). Except for pathological examination after resection, it is not known exactly whether LARC patients have achieved pathological complete response (pCR) before surgery. To date, there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes. AIM: To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC. METHODS: Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed. Patients were categorized into pCR and non-pCR groups. Univariate analysis (using the χ 2 test or Fisher's exact test) and logistic multivariate regression analysis were used to study clinical predictors affecting pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were calculated using Kaplan-Meier analysis, and differences in survival curves were assessed with the log-rank test. RESULTS: Univariate analysis showed that pretreatment carcinoembryonic antigen (CEA) level, lymphocyte-monocyte ratio (LMR), time interval between neoadjuvant therapy completion and total mesorectal excision, and tumor size were correlated with pCR. Multivariate results showed that CEA ≤ 5 ng/mL (P = 0.039), LMR > 2.73 (P = 0.023), and time interval > 10 wk (P = 0.039) were independent predictors for pCR. Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates (94.7% vs 59.7%, P = 0.002) and 5-year OS rates (95.8% vs 80.1%, P = 0.019) compared to the non-pCR group. Tumor deposits (TDs) were significantly correlated with shorter DFS (P = 0.002) and OS (P < 0.001). CONCLUSION: Pretreatment CEA, LMR, and time interval contribute to predicting nCRT efficacy in LARC patients. Achieving pCR demonstrates longer DFS and OS. TDs correlate with poor prognosis.

6.
Angew Chem Int Ed Engl ; : e202408527, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958191

ABSTRACT

Janus heterostructures consisting of multiple jointed components with distinct properties have gained growing interest in the photoredox catalytic field. Herein, we have developed a facile low-temperature method to gain anisotropic one-dimensional Au-tipped CdS (Au-CdS) nanorods (NRs), followed by assembling Ru molecular co-catalyst (RuN5) onto the surface of the NRs. The CdS NRs decorated with plasmonic Au nanoparticles (NPs) and RuN5 complex harness the virtues of metal-semiconductor and inorganic-organic interface, giving directional charge transfer channels, spatially separated reaction sites, and enhanced local electric field distribution. As a result, the Au-CdS-RuN5 can act as an efficient dual-function photocatalyst for simultaneous H2 evolution and valorization of biomass-derived alcohols. Benefiting from the interfacial charge decoupling and selective chemical bond activation, the optimal all-in-one Au-CdS-RuN5 heterostructure shows greatly enhanced photoactivity and selectivity as compared to bare CdS NRs, along with a remarkable apparent quantum yield of 40.2% at 400 nm. The structural evolution and working mechanism of the heterostructures are systematically analyzed based on experimental and computational results.

7.
Reprod Toxicol ; 128: 108659, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38972361

ABSTRACT

Oridonin, a natural terpenoid isolated from the leaves of Isodon rubescens (Hemsley) H.Hara, is widely used in oriental medicine for its anticancer properties across various cancer types. Despite its prevalent use, the toxic effects of oridonin on male reproduction, particularly its impact on sperm functions and the mechanisms involved, are not well understood. This study aimed to explore the effects and underlying mechanisms of oridonin on sperm functions. We initially treated Duroc boar spermatozoa with varying concentrations of oridonin (0, 5, 50, 75, 100, and 150 µM) and incubated them to induce capacitation. We then assessed cell viability and several sperm functions, including sperm motility and motion kinematics, capacitation status, and ATP levels. We also analyzed the expression levels of proteins associated with the phosphatidylinositol 3-kinase (PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/protein kinase B (AKT) signaling pathway and phosphotyrosine proteins. Our results indicate that oridonin adversely affects most sperm functions in a dose-dependent manner. We observed significant decreases in AKT, p-AKT (Thr308), phosphatase and tensin homolog (PTEN), p-PDK1, and p-PI3K levels following oridonin treatment, alongside an abnormal increase in phosphotyrosine proteins. These findings suggest that oridonin may disrupt normal levels of tyrosine-phosphorylated proteins by inhibiting the PI3K/PDK1/AKT signaling pathway, which is crucial for cell proliferation, metabolism, and apoptosis, thus potentially harming sperm functions. Consequently, we recommend considering the reproductive toxicity of oridonin when using it as a therapeutic agent.

8.
J Formos Med Assoc ; 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38880710

ABSTRACT

BACKGROUND PURPOSE: Capsule endoscopy (CE) is a noninvasive examination for excellent visualization of small bowel mucosal lesions. We aimed to evaluate the clinical efficacy and safety of CE in pediatric patients. METHODS: From April 2014 to December 2022, CE procedures performed in children younger than 18 years of age at Taichung Veteran General Hospital were analyzed retrospectively. RESULTS: Among 136 procedures, the completion rate was 95.6% (n = 130), with a median age of 14 years old. Suspicion or evaluation of inflammatory bowel diseases (IBD) (41%) was the most common indication for CE. Other common indications of CE were chronic unexplained abdominal pain (35%) and obscure gastrointestinal bleeding or iron deficiency anemia (21%). No procedure-related complications occurred. The diagnosis of those patients with incomplete study were CD with small bowel stricture, graft-versus-host disease and duodenal ulcers. A total of 86 CE procedures showed positive findings, and the overall diagnostic yield rate was 63.2%. Small bowel ulcers (65.12%) were the most common findings. Overall, 26.5% of CE examinations resulted in a new diagnosis and 44.9% of CE exams led to a change in therapy. For patients with IBD, CE findings resulted in an even higher therapeutic change rate of 48.1%. CONCLUSIONS: CE is a safe and feasible diagnostic method to study the small intestine in children, especially for IBD. Incomplete study could be an indicator of positive finding and can potentially be a guide to identify the site of possible strictures.

9.
Microorganisms ; 12(6)2024 May 24.
Article in English | MEDLINE | ID: mdl-38930445

ABSTRACT

Nitrile-containing insecticides can be converted into their amide derivatives by Pseudaminobacter salicylatoxidans. N-(4-trifluoromethylnicotinoyl) glycinamide (TFNG-AM) is converted to 4-(trifluoromethyl) nicotinoyl glycine (TFNG) using nitrile hydratase/amidase. However, the amidase that catalyzes this bioconversion has not yet been fully elucidated. In this study, it was discovered that flonicamid (FLO) is degraded by P. salicylatoxidans into the acid metabolite TFNG via the intermediate TFNG-AM. A half-life of 18.7 h was observed for P. salicylatoxidans resting cells, which transformed 82.8% of the available FLO in 48 h. The resulting amide metabolite, TFNG-AM, was almost all converted to TFNG within 19 d. A novel amidase-encoding gene was cloned and overexpressed in Escherichia coli. The enzyme, PmsiA, hydrolyzed TFNG-AM to TFNG. Despite being categorized as a member of the amidase signature enzyme superfamily, PsmiA only shares 20-30% identity with the 14 previously identified members of this family, indicating that PsmiA represents a novel class of enzyme. Homology structural modeling and molecular docking analyses suggested that key residues Glu247 and Met242 may significantly impact the catalytic activity of PsmiA. This study contributes to our understanding of the biodegradation process of nitrile-containing insecticides and the relationship between the structure and function of metabolic enzymes.

10.
Biomedicines ; 12(6)2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38927519

ABSTRACT

The present study evaluated the antiseizure and neuroprotective effects of sodium houttuyfonate (SH), a derivative of Houttuynia cordata Thunb. (H. cordata), in a kainic acid (KA)- induced seizure rat model and its underlying mechanism. Sprague Dawley rats were administered normal saline, SH (50 or 100 mg/kg), or carbamazepine (300 mg/kg) by oral gavage for seven consecutive days before the intraperitoneal administration of KA (15 mg/kg). SH showed antiseizure effects at a dose of 100 mg/kg; it prolonged seizure latency and decreased seizure scores. SH also significantly decreased neuronal loss in the hippocampi of KA-treated rats, which was associated with the prevention of glutamate level increase, the upregulation of glutamate reuptake-associated proteins (excitatory amino acid transporters 1-3), glutamate metabolism enzyme glutamine synthetase, the downregulation of the glutamate synthesis enzyme glutaminase, and significant alterations in the expression of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor) and NMDA (N-methyl-D-aspartic acid receptor) receptor subunits in the hippocampus. Furthermore, the effects of SH were similar to those of the antiseizure drug carbamazepine. Therefore, the results of the present study suggest that SH has antiseizure effects on KA-induced seizures, possibly through the prevention of glutamatergic alterations. Our findings suggest that SH is a potential alternative treatment that may prevent seizures by preserving the normal glutamatergic system.

11.
Ying Yong Sheng Tai Xue Bao ; 35(5): 1369-1378, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38886436

ABSTRACT

To explore the temporal and spatial variations in phytoplankton community in small estuaries, we collected surface water samples from Yongjiang River estuary during wet, normal, and dry seasons and determined the main driving factors of phytoplankton community. A total of 358 species belonging to nine phyla and 123 genera were identified in all seasons. During wet, normal, and dry seasons, species number was 276, 154 and 151, and the abundance was (170.45±225.43)×103, (51.92±30.28)×103 and (31.65±12.79)×103 cells·L-1, respectively. Diatoms dominated the phytoplankton community, and the main dominant species were Cyclotella meneghiniana, Skeletonema costatum, and Paralia sulcata. Shannon diversity and Pielou evenness indices decreased from inside mouth to outside mouth in wet season, but there was no obvious spatial difference in normal season or dry season. Results of non-metric multidimensional scaling analysis and analysis of similarities showed that phytoplankton community composition differed significantly among different regions (inside, at and outside mouth) and different seasons. In wet season, phytoplankton abundance was significantly positively correlated with temperature, dissolved inorganic nitrogen, and dissolved reactive phosphorus, but significantly negatively correlated with salinity. In normal season, phytoplankton abundance was significantly negatively correlated with temperature. In dry season, it was not significantly correlated with environmental factors. Results of redundancy analysis showed that temperature, salinity, ammonium and dissolved reactive phosphorus explained the variations in phytoplankton community by 19.5%, 11.9%, 9.4% and 8.2%, respectively. These results revealed high dominance of diatoms and the main driving factors (temperature, salinity and nutrients) of phytoplankton community in Yongjiang River estuary.


Subject(s)
Diatoms , Estuaries , Phytoplankton , Rivers , Seasons , Phytoplankton/growth & development , Phytoplankton/classification , China , Diatoms/growth & development , Diatoms/classification , Population Dynamics , Spatio-Temporal Analysis , Environmental Monitoring , Ecosystem , Nitrogen/analysis
12.
Healthcare (Basel) ; 12(11)2024 May 27.
Article in English | MEDLINE | ID: mdl-38891171

ABSTRACT

Home exercise programs are beneficial in managing frozen shoulder (FS), yet adherence remains challenging. This pilot study introduces the remote app, Defrozen, designed for home exercises and assesses its feasibility and clinical outcomes in FS patients undergoing intra-articular and sub-acromial corticosteroid treatment. Over a four-week period, patients used the Defrozen-app, engaging in guided exercises. The feasibility of the intervention was assessed through several measurement scales, including adherence, the Technology Acceptance Model 2 (TAM2), the System Usability Scale (SUS), and User Satisfaction and Engagement (USE). Clinical outcomes included pain scale, Oxford Shoulder Score (OSS), Quick Disability of the Arm, Shoulder, and Hand (QuickDASH) Score, and passive range of motion. The TAM2 results indicated high perceived usefulness (4.5/5), ease of use (4.8/5), and intention to use (4.4/5); the SUS score was high at 81.7/100, complemented by USE scores reflecting ease of learning (4.9/5) and satisfaction (4.3/5). Clinical outcomes showed significant pain reduction, improved shoulder function, reduced shoulder-related disability, and increased shoulder range of motion. These findings suggest the Defrozen-app as a promising solution for FS, significantly improving adherence and showing potential to enhance clinical outcomes. However, these clinical outcome results are preliminary and necessitate further validation through a large-scale randomized controlled trial to definitively confirm efficacy and assess long-term benefits.

14.
Colloids Surf B Biointerfaces ; 241: 113989, 2024 May 26.
Article in English | MEDLINE | ID: mdl-38838444

ABSTRACT

Icariin has been shown the promising therapeutic potential to treat inflammatory airway diseases, yet its poor lung distribution and retention restrict the clinical applications. To this end, this work aimed to prepare an icariin-phospholipid complex (IPC) formulation for sustained nebulization delivery that enabled excellent inhalability, improved lung exposure and prolonged duration of action. Icariin was found to react with soybean phospholipid to form supramolecular IPC, which was able to self-assemble into nanoparticle suspension. The suspension was stable during steam sterilization and nebulization processes, and its aerosols generated by a commercial nebulizer exhibited excellent aerodynamic properties and delivery efficiency. In vitro studies showed that the formation of complex sustained drug release, enhanced lung affinity and slowed lung clearance. The drug distribution in lung epithelial lining fluid (ELF) also demonstrated in vivo sustained release after intratracheal administration to mice. In addition, compared to free icariin, IPC improved the drug exposure to lung tissues and immune cells in the ELF by 4.61-fold and 39.5-fold, respectively. This resulted in improved and prolonged local anti-inflammatory effects up to 24 h in mice with lipopolysaccharide (LPS)-induced acute lung injury. Moreover, IPC improved survival rate of mice with acute respiratory distress syndrome (ARDS). Overall, the present phospholipid complex represented a promising formulation of icariin for the treatment of acute lung injury/ARDS by nebulization delivery.

15.
Haematologica ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38841794

ABSTRACT

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

16.
Appl Opt ; 63(12): 3108-3116, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38856454

ABSTRACT

In general, visible light communication (VLC) uses LEDs as transmitters. However, LEDs can serve as receivers to construct a simple duplex VLC system that uses only two LEDs instead of one LED and one photo-diode (PD). There is a lack of effective equivalent analysis models for characterizing and evaluating the inherent behavioral characteristics of LEDs used as receivers. This paper presents an equivalent analysis model for GaN LEDs as receivers. First, based on the proposed receiving equivalent circuit model, a third-order signal transmission mathematical analysis model is established, revealing the transmission relationship between the photocurrent and output voltage. Further research is conducted on the impact of parameter changes on the bandwidth, and the model can be simplified into a first-order low-pass mathematical analysis model under specific conditions, providing theoretical support for improving the bandwidth of LED receiving applications. The experimental results also confirm the theoretical predictions. This research result holds significant importance for revealing the intrinsic mechanisms and the improved optical communication performance of LEDs for effective reception.

17.
Cell Discov ; 10(1): 70, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38937452

ABSTRACT

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants. TKD is composed of a KRAS-binding nanobody, a cell-penetrating peptide selectively targeting cancer cells, and a lysosome-binding motif. Our data revealed that TKD selectively binds to KRAS in cancer cells and effectively induces KRAS degradation via a lysosome-dependent process. Functionally, TKD suppresses tumor growth with no obvious side effects and enhances the antitumor effects of PD-1 antibody and cetuximab. This study not only provides a strategy for developing drugs targeting "undruggable" proteins but also reveals that TKD is a promising therapeutic for treating KRAS-mutant cancers.

19.
Geroscience ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822946

ABSTRACT

Considerable uncertainty remains regarding the associations of multiple factors with brain health. We aimed to conduct an exposome-wide association study on neurodegenerative disease and neuropsychiatry disorders using data of participants from the UK Biobank. Multivariable Cox regression models with the least absolute shrinkage and selection operator technique as well as principal component analyses were used to evaluate the exposures in relation to common disorders of central nervous system (CNS). Restricted cubic splines were conducted to explore potential nonlinear correlations. Then, weighted standardized scores were generated based on the coefficients to calculate the joint effects of risk factors. We also estimated the potential impact of eliminating the unfavorable profiles of risk domains on CNS disorders using population attributable fraction (PAF). Finally, sensitivity analyses were performed to reduce the risk of reverse causality. The current study discovered the significantly associated exposures fell into six primary exposome categories. The joint effects of identified risk factors demonstrated higher risks for common disorders of CNS (HR = 1.278 ~ 3.743, p < 2e-16). The PAF varied by exposome categories, with lifestyle and medical history contributing to majority of disease cases. In total, we estimated that up to 3.7 ~ 64.1% of disease cases could be prevented.This study yielded modifiable variables of different categories and assessed their joint effects on common disorders of CNS. Targeting the identified exposures might help formulate effective strategies for maintaining brain health.

20.
Ther Adv Hematol ; 15: 20406207241256894, 2024.
Article in English | MEDLINE | ID: mdl-38828002

ABSTRACT

Background: Pediatric acute myeloid leukemia (AML) has poor prognosis and high rate of relapse and mortality, and exploration of new treatment options is still critically needed. Objectives: To summarize the outcome of our new treatment strategies for pediatric AML, which is characterized by dual induction and acute lymphoblastic leukemia (ALL) elements consolidation. Design: Retrospective, single-arm study. Methods: From July 2012 to December 2019, an intensive chemotherapy protocol was used for newly diagnosed children with AML, which contains dual induction, three courses of consolidations based on high-dose cytarabine, and two courses of consolidations composed of high-dose methotrexate, vincristine, asparaginase, and mercaptopurine (ALL-like elements). Blasts were monitored by bone marrow smears at intervals, and two lumbar punctures were performed during chemotherapy. We retrospectively analyzed the efficacy and safety of this study. The last follow-up was on 26 May 2023. Results: A total of 70 pediatric AMLs were included. The median age at diagnosis was 6.7 (0.5-16.0) years. The median initial WBC count was 23.74 × 109/L, 11 of whom ⩾100 × 109/L. After dual induction, there were 62 cases of complete remission (CR), 5 cases of partial remission, and 3 cases of nonremission. The CR rate was 88.57%. The median follow-up time was 5.8 (0.2-9.4) years, the 5-year overall survival was 78.2% ± 5%, the event-free survival (EFS) was 71.2% ± 5.6%, and the cumulative recurrence rate was 27.75%. The 5-year EFS of patients with initial WBC < 100 × 109/L (n = 59) and ⩾100 × 109/L (n = 11) were 76.4% ± 5.7% and 45.5% ± 15% (p = 0.013), respectively. A total of 650 hospital infections occurred. The main causes of infection were respiratory tract infection (26.92%), septicemia (18.46%), stomatitis (11.85%), and skin and soft-tissue infection (10.46%). Conclusion: This intensive treatment protocol with dual induction and ALL-like elements is effective and safe for childhood AML. Initial WBC ⩾ 100 × 109/L was the only independent risk factor in this cohort. Trial registration: It is a retrospective study, and no registration on ClinicalTrials.gov.

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