To enhance the therapeutic efficacy of the baicalin-berberine complex(BA-BBR) in the treatment of ulcerative colitis(UC), BA-BBR nanocrystal microspheres(BA-BBR NC MS) were prepared using the dropping method. The microspheres were characterized in terms of morphology, particle size, differential scanning calorimetry(DSC), and powder X-ray diffraction(XRD). The release profiles of BA and BBR from the microspheres were measured, and the drug release mechanism was investigated. A rat model of UC was induced by 5% dextran sodium sulfate(DSS) and treated continuously for 7 days to evaluate the therapeutic effects of different formulations. The results showed that the prepared BA-BBR MS and BA-BBR NC MS were uniform gel spheres with particle sizes of(1.77±0.16) mm and(1.67±0.08) mm, respectively. After drying, the gels collapsed inward and exhibited a rough surface. During the preparation process, the BA-BBR nanocrystals(BA-BBR NC) were uniformly encapsulated within the microspheres. The release profiles of the microspheres followed a first-order kinetic model, and the 12-hour cumulative release of BA and BBR from BA-BBR NC MS was higher than that from BA-BBR MS. Compared with BA-BBR, BA-BBR NC, and BA-BBR MS, BA-BBR NC MS further alleviated UC symptoms in rats, most significantly reducing the levels of TNF-α, IL-1β, IL-6, and MPO, while increasing the level of IL-4 in colon tissues. These results indicate that BA-BBR NC MS, based on a "nano-in-micro" design, can deliver BA-BBR to the intestine and exert significant therapeutic effects in a UC rat model, suggesting it as a promising new strategy for the treatment of UC.
Animals ; Colitis, Ulcerative/metabolism* ; Rats ; Nanoparticles/chemistry* ; Microspheres ; Male ; Berberine/administration & dosage* ; Flavonoids/administration & dosage* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Particle Size ; Tumor Necrosis Factor-alpha/immunology* ; Drug Liberation ; Drug Compounding

OBJECTIVE: This study examines utilizes the advantages of machine learning algorithms to discern key determinants in prognosticate postoperative circulatory complications (PCCs) for older patients. METHODS: This secondary analysis of data from a randomized controlled trial involved 1,720 elderly participants in five tertiary hospitals in Beijing, China. Participants aged 60-90 years undergoing major non-cardiac surgery under general anesthesia. The primary outcome metric of the study was the occurrence of PCCs, according to the European Society of Cardiology and the European Society of Anaesthesiology diagnostic criteria. The analysis metrics contained 67 candidate variables, including baseline characteristics, laboratory tests, and scale assessments. RESULTS: Our feature selection process identified key variables that significantly impact patient outcomes, including the duration of ICU stay, surgery, and anesthesia; APACHE-II score; intraoperative average heart rate and blood loss; cumulative opioid use during surgery; patient age; VAS-Move-Median score on the 1st to 3rd day; Charlson comorbidity score; volumes of intraoperative plasma, crystalloid, and colloid fluids; cumulative red blood cell transfusion during surgery; and endotracheal intubation duration. Notably, our Random Forest model demonstrated exceptional performance with an accuracy of 0.9872. CONCLUSION We have developed and validated an algorithm for predicting PCCs in elderly patients by identifying key risk factors.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Cardiovascular Diseases/etiology* ; Machine Learning ; Postoperative Complications/etiology* ; Risk Factors ; Randomized Controlled Trials as Topic ; Secondary Data Analysis

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective: To analyze the results of national external quality assessment (EQA) for transfusion compatibility test from 2018 to 2023, with the aim of providing references for improving laboratory testing quality and ensuring the safety of clinical blood transfusion. Methods: Three EQA programs were conducted annually, each distributing 22 quality assessment samples. Participating transfusion laboratories were required to complete testing within specified deadlines and to submit results along with documentation of testing methodologies, reagents, and equipment used. National Center for Clinical Laboratories (NCCL) conducted statistical analysis of laboratory results, evaluated testing outcomes and related circumstances, and provided feedback to participating laboratories. EQA data from transfusion laboratories across China from 2018 to 2023 were collected and systematically analyzed. Results: From 2018 to 2023, the qualification rates for all five items (ABO forward typing, ABO reverse typing, Rh blood group typing, antibody screening, and cross-matching) were 67.59%, 77.11%, 77.38%, 72.78%, 79.96%, and 85.16%, respectively. The mean qualification rates for ABO forward typing, ABO reverse typing, RhD blood group typing, antibody screening, and cross-matching over the past six years were 96.25%±0.59%, 90.45%±4.52%, 96.05%±0.71%, 90.88%±2.86%, and 88.34%±3.48%, respectively. The qualification rates in 2019, 2020, 2022, and 2023 all showed a stable trend of "blood stations>tertiary hospitals>secondary hospitals". The mean qualification rate of laboratories in secondary hospitals from 2018 to 2023 was significantly lower than those of laboratories in tertiary hospitals and blood stations (P<0.05), while no significant difference was observed between laboratories in tertiary hospitals and blood stations (P>0.05). The micro column agglutination method was the most widely used in all five tests. In the four test items, namely ABO forward typing, ABO reverse typing, antibody screening, and cross-matching, there was a statistically significant difference in the qualification rate of micro column agglutination method compared to other methods (P<0.05). There was a statistical difference in the qualification rate between manual and automated detection using micro column agglutination method in the cross-matching tests (P<0.05), whereas no significant difference was noted for the other test items (P>0.05). Conclusion: From 2018 to 2023, the number of laboratories participating in EQA activities has been increasing year by year, and the qualification rate has shown an overall upward trend. The type of laboratory is a key factor affecting the qualification rate, and the testing capabilities of some laboratories still need to be improved. The micro column agglutination method is widely used in transfusion compatibility tests. The established EQA program effectively monitors quality issues in laboratories, drives continuous improvement, and ensures sustained enhancement of testing standards to safeguard clinical blood safety.

Objective To investigate the relationship between the serum FMS-like tyrosine kinase 3 ligand(Flt3L),progranulin(PGRN)levels and the disease risk and disease outcome of patients with acute lympho-blastic leukemia(ALL).Methods A total of 104 patients with ALL admitted to the hospital from September 2019 to September 2021 were selected as the research subjects.ALL patients were divided into the low-risk group(n=34),the medium-risk group(n=39),and the high-risk group(n=31)according to the disease risk.The levels of serum Flt3L and PGRN of the patients at admission were detected by enzyme-linked immu-nosorbent assay.Pearson correlation analysis was used to analyze the relationship between serum Flt3L,PGRN in ALL patients and the risk of ALL disease.According to the follow-up results of ALL patients,they were divided into the good prognosis group(n=81)and the poor prognosis group(n=23).The receiver oper-ating characteristic curve and the area under the curve(AUC)were used to analyze the evaluation value of se-rum Flt3L and PGRN for the prognosis of ALL patients,and multivariate Cox regression was used to analyze the prognostic risk factors of ALL patients.Results The serum Flt3L levels in the low-risk group and the medium-risk group were higher than those in the high-risk group,and the difference was statistically signifi-cant(P＜0.05).The serum PGRN levels in the low-risk group and the medium-risk group were lower than those in the high-risk group,and the difference was statistically significant(P＜0.05).Serum Flt3L in ALL patients was negatively correlated with the risk of ALL disease(r=-0.461,0.593,P＜0.05).Serum PGRN in ALL patients was positively correlated with the risk of ALL disease(r=0.593,P＜0.05).The proportions of white blood cell count ≥50 × 109/L,hemoglobin＜90 g/L,and serum PGRN level in the poor prognosis group were higher than those in the good prognosis group,while the serum Flt3L level was lower than that in the good prognosis group,and the differences were statistically significant(P＜0.05).The AUC of serum Flt3L and PGRN in evaluating the prognosis of ALL patients were 0.762(95％CI:0.717-0.816),0.815(95％CI:0.764-0.863),and 0.915(95％CI:0.866-0.964),respectively.White blood cell count ≥50 × 109/L,hemoglobin＜90 g/L,Flt3L＜92.07 pg/mL,and PGRN≥335.14 pg/mL were risk factors affecting the prognosis of ALL patients(P＜0.05).Conclusion The levels of serum Flt3L and PGRN in ALL patients are related to the disease risk and disease outcome of ALL.The combined detection of the two has a good eval-uation value for the prognosis of adult ALL patients.

Objective:To construct and evaluate the nomogram prediction model of spontaneous rupture of primary liver cancer (STRPLC), and make the web-based dynamic online nomogram.Methods:Clinical data of 346 patients with PLC treated in the Second Affiliated Hospital of Kunming Medical University were retrospectively analyzed, including 87 males and 15 females, aged 58.15±10.32 years. Single factor and multiple factor logistic regression analysis were used to screen the influencing factors of STRPLC, and the prediction model was constructed based on the nomogram. Receiver operating characteristic (ROC) curve, calibration curve and clinical decision analysis were used to evaluate the model. The web-based dynamic online nomogram was developed using the DynNom package in R4.3.1 software.Results:Multivariate logistic regression analysis showed that the independent risk factors for spontaneous rupture and hemorrhage of tumor were no history of systematic anti-tumor therapy, alpha-fetoprotein (AFP) level, tumor protrusion on liver surface, tumor length, invasion of major blood vessels, and moderate to large amount of ascites (all P<0.05). The area under the receiver operating characteristic curve (AUC) of the prediction model constructed by this nomogram is 0.913 (95% CI: 0.884-0.943), the best cutoff value is 0.254, with a sensitivity of 0.892, and a specificity of 0.803. The calibration curve shows a good agreement between the predicted probability and the actual probability. The decision curve of the model is above the two invalid lines of " none" and " all" in the horizontal range of 0.07-0.98, and the clinical net benefit of the model is >0. Then user-friendly web-based dynamic online nomogram is constructed. Conclusion:Large tumor size, superficial location, no history of systematic anti-tumor therapy, high AFP level, invasion of major blood vessels, and moderate to large amount of ascites are independent risk factors for STRPLC. The prediction model and dynamic online nanogram constructed by this method can effectively assess the risk of STRPLC.

OBJECTIVE: To investigate the effectiveness of digital three-dimensional (3D) assisted unilateral biportal endoscopy (UBE) in the treatment of highly isolated lumbar disc herniation (LDH) with translaminar approach. METHODS: The clinical data of 59 patients who met the selection criteria and underwent UBE treatment due to highly isolated LDH between January 2022 and December 2023 were retrospectively analyzed. Among them, 25 cases were treated with digital 3D assisted translaminar approach (observation group) and 34 cases were treated with interlaminar approach (control group). There was no significant difference in gender, age, disease duration, surgical segment, and preoperative visual analogue scale (VAS) score and Oswestry disability index (ODI) between the two groups ( P>0.05). The operation time, intraoperative blood loss, and lateral articular surface preservation rate were recorded and compared between the two groups. VAS score and ODI were used to evaluate the improvements of pain and function before operation and at 3 and 6 months after operation. The modified MacNab criteria was used to evaluate the effectiveness at last follow-up. RESULTS: One patient in the control group had dural tear, and the other patients had no nerve injury, infection, dural tear, or other related complications. There was no significant difference in operation time and intraoperative blood loss between the two groups ( P>0.05). Patients in both groups were followed up 6-13 months, with an average of 8.3 months. The lateral articular surface preservation rate in the observation group was significantly higher than that in the control group ( P<0.05). Three patients in the observation group and 2 patients in the control group had calf muscle venous thrombosis, which was cured after anticoagulant treatment with rivaroxaban and delayed exercise time. There was no recurrence or second operation during the follow-up period. The VAS score and ODI of the two groups at 3 and 6 months after operation significantly improved when compared with those before operation ( P<0.05). There was no significant difference between the two groups at each time point after operation ( P>0.05). At last follow-up, the effectiveness was evaluated according to the modified MacNab criteria, and there was no significant difference in the evaluation grade and excellent and good rate between the two groups ( P>0.05). CONCLUTION UBE via translaminar approach is safe and effective for the treatment of highly isolated LDH, which is beneficial to protect the facet joint, maintain spinal stability, and reduce soft tissue injury. With the assistance of digital 3D technique, preoperative planning can be performed accurately.
Humans ; Intervertebral Disc Displacement/diagnostic imaging* ; Lumbar Vertebrae/diagnostic imaging* ; Male ; Retrospective Studies ; Female ; Endoscopy/methods* ; Treatment Outcome ; Middle Aged ; Adult ; Imaging, Three-Dimensional ; Operative Time ; Pain Measurement

OBJECTIVES: To investigate the relationship between the polygenic risks for various psychiatric disorders and clinical and neuropsychological characteristics in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Using a cross-sectional design, 285 children with ADHD and 107 healthy controls were assessed using the Child Behavior Checklist, the Behavior Rating Inventory of Executive Function for parents, the Wechsler Intelligence Scale for Children, Fourth Edition, and the Cambridge Neuropsychological Test Automated Battery. Blood samples were collected for genetic data. Polygenic risk scores (PRSs) for various psychiatric disorders were calculated using the PRSice-2 software. RESULTS: Compared with the healthy controls, the children with ADHD displayed significantly higher PRSs for ADHD, major depressive disorder, anxiety disorder, and obsessive-compulsive disorder (P<0.05). In terms of daily-life executive function, ADHD-related PRS was significantly correlated with the working memory factor; panic disorder-related PRS was significantly correlated with the initiation factor; bipolar disorder-related PRS was significantly correlated with the shift factor; schizophrenia-related PRS was significantly correlated with the inhibition, emotional control, initiation, working memory, planning, organization, and monitoring factors (P<0.05). The PRS related to anxiety disorders was negatively correlated with total IQ and processing speed index (P<0.05). The PRS related to obsessive-compulsive disorder was negatively correlated with the processing speed index and positively correlated with the stop-signal reaction time index of the stop-signal task (P<0.05). CONCLUSIONS PRSs for various psychiatric disorders are closely correlated with the behavioral and cognitive characteristics in children with ADHD, which provides more insights into the heterogeneity of ADHD.
Humans ; Attention Deficit Disorder with Hyperactivity/genetics* ; Child ; Male ; Female ; Cross-Sectional Studies ; Neuropsychological Tests ; Multifactorial Inheritance ; Adolescent ; Mental Disorders/etiology* ; Executive Function ; Genetic Risk Score

OBJECTIVES: To explore the expression profile of circular RNAs (circRNAs) and their potential roles in prognosis and progression of Wilms' tumor (WT). METHODS: Four pairs of WT and adjacent tissues were collected for high-throughput circRNA sequencing to identify the differentially expressed circular RNAs. RT-qPCR was used to verify the expression levels of the top 6 candidate circRNAs in the clinical samples. hsa_circ_0001900 was selected for analysis of its correlation with clinicopathological features and prognosis in 34 patients with WT. Sanger sequencing and RNase R digestion experiments were used to verify the cycling site and structural stability of hsa_circ_0001900 molecule. RESULTS: A total of 23 978 circular RNA molecules were identified in WT tissues by high-throughput circular RNA sequencing, and among them 614 were differentially expressed in WT. hsa_circ_0001900 showed the highest expression level among the differentially expressed circRNAs, which was consistent with the findings in clinical tumor samples and the sequencing results. Correlation analysis showed that hsa_circ_0001900 expression level was positively correlated with WT volume, and the children with high hsa_circ_0001900 expression had a lowered recurrence-free survival rate. The results of Sanger sequencing verified the circular splice site sequence of the molecule, and Rnase R digestion assay confirmed its stable covalent structure. CONCLUSIONS This study presents a comprehensive expression profile of circular RNAs in WT, and the expression level of hsa_circ_0001900 is related to the size of WT and the patients' prognosis, suggesting its possible role as a key driving gene in WT progression.
Humans ; RNA, Circular ; Wilms Tumor/pathology* ; Prognosis ; High-Throughput Nucleotide Sequencing ; Kidney Neoplasms/genetics* ; Sequence Analysis, RNA ; Male ; Female

Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome, with implications for microbial pathogenesis and host defense. Among these, transfer RNA-derived small RNAs (tsRNAs) have garnered attention for their roles in modulating microbial behavior. However, the bacterial factors mediating tsRNA interaction and functionality remain poorly understood. In this study, using RNA affinity pull-down assay in combination with mass spectrometry, we identified a putative membrane-bound protein, annotated as P-type ATPase transporter (PtaT) in Fusobacterium nucleatum (Fn), which binds Fn-targeting tsRNAs in a sequence-specific manner. Through targeted mutagenesis and phenotypic characterization, we showed that in both the Fn type strain and a clinical tumor isolate, deletion of ptaT led to reduced tsRNA intake and enhanced resistance to tsRNA-induced growth inhibition. Global RNA sequencing and label-free Raman spectroscopy revealed the phenotypic differences between Fn wild type and PtaT-deficient mutant, highlighting the functional significance of PtaT in purine and pyrimidine metabolism. Furthermore, AlphaFold 3 prediction provides evidence supporting the specific binding between PtaT and Fn-targeting tsRNA. By uncovering the first RNA-binding protein in Fn implicated in growth modulation through interactions with host-derived small RNAs (sRNAs), our study offers new insights into sRNA-mediated host-pathogen interplay within the context of microbiome-host interactions.
Fusobacterium nucleatum/growth & development* ; RNA-Binding Proteins/genetics* ; Bacterial Proteins/genetics* ; RNA, Bacterial/metabolism* ; Humans ; RNA, Transfer/metabolism*