Accelerated Discovery of Carbamate Cbl-b Inhibitors Using Generative AI Models and Structure-Based Drug Design.

Casitas B-lymphoma proto-oncogene-b (Cbl-b) is a RING finger E3 ligase that has an important role in effector T cell function, acting as a negative regulator of T cell, natural killer (NK) cell, and B cell activation. A discovery effort toward Cbl-b inhibitors was pursued in which a generative AI design engine, REINVENT, was combined with a medicinal chemistry structure-based design to discover novel inhibitors of Cbl-b. Key to the success of this effort was the evolution of the "Design" phase of the Design-Make-Test-Analyze cycle to involve iterative rounds of an in silico structure-based drug design, strongly guided by physics-based affinity prediction and machine learning DMPK predictive models, prior to selection for synthesis. This led to the accelerated discovery of a potent series of carbamate Cbl-b inhibitors.

How specific ion effects influence the mechanical behaviors of amide macromolecules? A cross-scale study.

The mechanisms of specific ion effects on the properties of amide macromolecules is essential to understanding the evolution of life. Because most biological macromolecules contain both complex hydrophilic and hydrophobic structures, it is challenging to accurately identify the contributions of molecular structure to macroscopic behaviors. Herein, we investigated the influence of specific ion effects on the mechanical behaviors of poly(N-isopropylacrylamide) and neutral polyacrylamide (i.e., PNIPAM and NPAM), through a cross-scale study that includes single-molecule force spectroscopy, molecular dynamics simulation and macro mechanical method. The results indicate that the molecular conformation can be markedly influenced by the hydrophilicity (or hydrophobicity) of both macromolecule chain and ions. An extended chain conformation can be obtained when the side groups and ions are relatively hydrophilic, which can also increase the elasticity of a macromolecule chain and film materials. The relatively hydrophobic components promote the collapse of macromolecule chains and reduce the molecular elasticity. It is believed that the hydrogen bonding intensity between a macromolecule chain and aquated ions controls the chain conformation and the elasticity of molecules and films. This study is not only helpful for understanding the self-assembly mechanism of organisms but also provides a way to associate the molecular properties with the macroscopic performance of materials.

Declined intrinsic capacity predicts long-term mortality in Chinese older adults: Beijing Longitudinal Study of Aging.

BACKGROUND: Intrinsic capacity reflects an individual's functions and capacities across their lifetime. There are few studies on whether the level of intrinsic capacity can predict long-term mortality in Chinese populations. OBJECTIVE: To explore the effects of intrinsic capacity on long-term outcomes in older Chinese adults. METHODS: Data were obtained from the Beijing Longitudinal Study of Aging. Overall, 1699 community-dwelling adults aged ≥60 years were included and followed up for 8 years. Intrinsic capacity was determined according to the World Health Organization definition. The predictive ability for adverse outcomes was assessed using the age- and sex-adjusted Cox proportional hazards model. RESULTS: A decline in intrinsic capacity domains was observed in 729 (42.9 %) participants. Declines in the mobility, cognition, vitality, sensory and psychology domains were observed in 21.8 %, 15.1 %, 11.4 %, 9.10 %, and 14.2 % of the participants, respectively. Low intrinsic capacity was associated with worse physical performance, frailty, social frailty, chronic diseases, fracture, and falls. A greater decline in intrinsic capacity predicted an elevated 8-year mortality rate (decline in overall intrinsic capacity hazard ratio 2.91, 95 % confidence interval 2.44-3.47, P < 0.001; decline in one domain hazard ratio 2.11, 95 % confidence interval 1.71-2.61, P < 0.001; decline in two domains hazard ratio 3.54, 95 % confidence interval 2.81-4.45, P < 0.001; decline in three or more domains hazard ratio 5.30, 95 % confidence interval 4.09-6.87, P < 0.001); adjusted models did not affect prediction performance. Among the five domains of intrinsic capacity, cognition was the strongest predictor of mortality (hazard ratio 3.17, 95 % confidence interval 2.63-3.81, P < 0.001). CONCLUSIONS: Intrinsic capacity is useful in identifying older adults at higher risk of adverse outcomes, presenting significant implications for healthcare policies in China.

The predictive value of thromboelastography, routine blood indices, ultrasound parameters, and placental thickness in determining fetal outcome.

OBJECTIVE: To evaluate the predictive value of thromboelastography, routine blood indices, ultrasound measurements, and placental thickness for fetal outcome. METHODS: A retrospective analysis of 218 expectant mothers at our hospital from April 2020 to June 2022 was conducted. Mothers were classified into favorable (n=164) and adverse (n=54) fetal outcome groups. We compared thromboelastography, blood counts, and ultrasound parameters, including placental thickness, between the two groups. Predictive models using lasso regression were developed for individual assessment type and their combinations. Model efficacies were evaluated by ROC curves and Delong's test. RESULTS: Thromboelastography indicated significantly higher values of R (P=0.004), Angle (P<0.001), and MA (P=0.002) while notably lower K (P<0.001) in the adverse outcome group compared to the favorable outcome group. Peripheral blood analysis showed elevated levels of WBC (P<0.001), CRP (P=0.001), and PLR (P<0.001) in the adverse outcome group. Ultrasound assessments revealed significant increases in S/D (P<0.001), PI (P=0.016), RI (P<0.001), and placental thickness (P<0.001) in the adverse outcome group. The areas under the curve (AUCs) for the thromboelastography (4 features), peripheral blood indices (3 features), ultrasound parameters (4 features), and combined index model (11 features) were 0.774, 0.779, 0.961, and 0.978, respectively. Delong's test indicated that the combined model's AUC did not significantly differ from that of the ultrasound parameters (P>0.05) but was superior to the models based on thromboelastography, peripheral blood indices, and placental thickness alone (P<0.001). CONCLUSION: This study underscores the unparalleled predictive value of ultrasound metrics in identifying the risk of adverse pregnancy outcomes, highlighting their critical role in prenatal risk assessment and monitoring frameworks.

[Clinical and genetic characteristics of a case of primary ciliary dyskinesia caused by new frameshift mutation of the DNAH5 gene].

OBJECTIVE: To investigate the clinical and genetic characteristics of a case of primary ciliary dyskinesia (PCD). METHODS: We collected the clinical data on a case of PCD treated in the Department of Reproductive Medicine of Linyi People's Hospital in July 2020, detected the genes of the patient by whole-exome sequencing (WES), verified the candidate mutations by Sanger sequencing, and predicted the protein structure of the mutant gene by SWISS-MODEL. RESULTS: The proband was found with the clinical phenotypes of chronic rhinitis, bronchiectasis, visceral transposition and male infertility. WES revealed a homozygous frameshift variation of c.12890dup (p.N4297Kfs*13) in exon 74 of the DNAH5 gene, which led to the premature termination of polypeptide chain synthesis and affected the gene function. SWISS-MODEL prediction showed that some of the amino acid residues were deleted after mutation, resulting in a 3D conformational change of the protein. This variation was not recorded in the ClinVar, gnomAD and OMIM databases and, according to the relevant guidelines of the American College of Genetics and Genomics, was classified as a pathogenic variation (PVS1+PM2_P+PM3_P). CONCLUSION: The homozygous variation of the DNAH5 gene c.12890dup (p.N4297Kfs*13) may be the cause of the clinical phenotype of this case of PCD, and the above findings have enriched the variation spectrum of the DNAH5 gene.

Study on the expression patterns of inner root sheath-specific genes in Tan sheep hair follicle during different developmental stages.

By analyzing the expression patterns of inner root sheath (IRS) specific genes during different developmental stages of hair follicle (HF) in Tan sheep embryos and at birth, this study aims to reveal the influence of the IRS on crimped wool. Skin tissues from the scapular region of male Tan sheep were collected at 85 days (E85) and 120 days (E120) of fetal development, and at 0 days (D0), 35 days (D35), and 60 days (D60) after birth, with four samples at each stage. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to determine the relative expression levels of IRS type I keratin genes (KRT25, KRT26, KRT27, KRT28), type II keratin genes (KRT71, KRT72, KRT73, KRT74), and the trichohyalin gene (TCHH) in the skin of Tan sheep at different stages. Results showed that the expression levels of all IRS-specific genes peaked at D0, with the expression of all genes significantly higher than at E85 (P < 0.01), except for KRT73 and TCHH. The expression levels of KRT25, KRT26, and KRT72 were also significantly higher than at E120 (P < 0.01). Furthermore, the expression levels of KRT27, KRT28, KRT71, and KRT74 were significantly higher than both at E120 and D35 (P < 0.01). The expression levels of other genes at different stages showed no significant difference (P > 0.05). Conclusion: The IRS-specific genes exhibit the highest expression levels in Tan sheep at the neonatal stage. The expression levels of KRT71, KRT72, and TCHH, which are consistent with the pattern of wool crimp, may influence the morphology of the IRS and thereby affect the crimp of Tan sheep wool.

Employing antagonistic C-X-C motif chemokine receptor 4 antagonistic peptide functionalized NaGdF4 nanodots for magnetic resonance imaging-guided biotherapy of breast cancer.

C-X-C motif chemokine receptor 4 (CXCR4) is a promising therapeutic target of breast cancer because it is overexpressed on cell surface of all molecular subtypes of breast cancer including triplenegative breast cancer (TNBC). Herein, CXCR4 antagonistic peptide-NaGdF4 nanodot conjugates (termed as anti-CXCR4-NaGdF4 NDs) have been constructed for magnetic resonance imaging (MRI)-guided biotherapy of TNBC through conjugation of the C-X-C Motif Chemokine 12 (CXCL12)-derived cyclic peptide with tryptone coated NaGdF4 nanodots (5 ± 0.5 nm in diameter, termed as Try-NaGdF4 NDs). The as-prepared anti-CXCR4-NaGdF4 NDs exhibits high longitudinal relaxivity (r1) value (21.87 mM-1S-1), reasonable biocompatibility and good tumor accumulation ability. The features of anti-CXCR4-NaGdF4 NDs improve the tumor-MRI sensitivity and facilitate tumor biotherapy after injection in mouse-bearing MDA-MB-231 tumor model in vivo. MRI-guided biotherapy using anti-CXCR4-NaGdF4 NDs enables to suppress 46% tumor growth. In addition, about 47% injection dose of anti-CXCR4-NaGdF4 NDs is found in the mouse urine at 24 h post-injection. These findings demonstrate that anti-CXCR4-NaGdF4 NDs enable to be used as renal clearable nanomedicine for biotherapy and MRI of breast cancer.

A hybrid evaluation of the intestinal absorption performance of compounds from molecular structure.

Intestinal absorption of compounds is significant in drug research and development. To evaluate this efficiently, a method combining mathematical modeling and molecular simulation was proposed, from the perspective of molecular structure. Based on the quantitative structure-property relationship study, the model between molecular structure and their apparent permeability coefficients was successfully constructed and verified, predicting intestinal absorption of drugs and interpreting decisive structural factors, such as AlogP98, Hydrogen bond donor and Ellipsoidal volume. The molecules with strong lipophilicity, less hydrogen bond donors and receptors, and small molecular volume are more easily absorbed. Then, the molecular dynamics simulation and molecular docking were utilized to study the mechanism of differences in intestinal absorption of drugs and investigate the role of molecular structure. Results indicated that molecules with strong lipophilicity and small volume interacted with the membrane at a lower energy and were easier to penetrate the membrane. Likewise, they had weaker interaction with P-glycoprotein and were easier to escape from it and harder to export from the body. More in, less out, is the main reason these molecules absorb well.

Detection and severity assessment of obstructive sleep apnea according to deep learning of single-lead electrocardiogram signals.

Developing a convenient detection method is important for diagnosing and treating obstructive sleep apnea. Considering availability and medical reliability, we established a deep-learning model that uses single-lead electrocardiogram signals for obstructive sleep apnea detection and severity assessment. The detection model consisted of signal preprocessing, feature extraction, time-frequency domain information fusion, and classification segments. A total of 375 patients who underwent polysomnography were included. The single-lead electrocardiogram signals obtained by polysomnography were used to train, validate and test the model. Moreover, the proposed model performance on a public dataset was compared with the findings of previous studies. In the test set, the accuracy of per-segment and per-recording detection were 82.55% and 85.33%, respectively. The accuracy values for mild, moderate and severe obstructive sleep apnea were 69.33%, 74.67% and 85.33%, respectively. In the public dataset, the accuracy of per-segment detection was 91.66%. A Bland-Altman plot revealed the consistency of true apnea-hypopnea index and predicted apnea-hypopnea index. We confirmed the feasibility of single-lead electrocardiogram signals and deep-learning model for obstructive sleep apnea detection and severity evaluation in both hospital and public datasets. The detection performance is high for patients with obstructive sleep apnea, especially those with severe obstructive sleep apnea.

Design of a water-soluble transmembrane receptor kinase with intact molecular function by QTY code.

Membrane proteins are critical to biological processes and central to life sciences and modern medicine. However, membrane proteins are notoriously challenging to study, mainly owing to difficulties dictated by their highly hydrophobic nature. Previously, we reported QTY code, which is a simple method for designing water-soluble membrane proteins. Here, we apply QTY code to a transmembrane receptor, histidine kinase CpxA, to render it completely water-soluble. The designed CpxAQTY exhibits expected biophysical properties and highly preserved native molecular function, including the activities of (i) autokinase, (ii) phosphotransferase, (iii) phosphatase, and (iv) signaling receptor, involving a water-solubilized transmembrane domain. We probe the principles underlying the balance of structural stability and activity in the water-solubilized transmembrane domain. Computational approaches suggest that an extensive and dynamic hydrogen-bond network introduced by QTY code and its flexibility may play an important role. Our successful functional preservation further substantiates the robustness and comprehensiveness of QTY code.

Efficacy of hysteroscopic levonorgestrel­releasing intrauterine device fixation in the treatment of adenomyosis: A cohort study.

The present study aimed to investigate the efficacy of hysteroscopic levonorgestrel-releasing intrauterine device (LNG-IUD) fixation surgery in the treatment of adenomyosis through a cohort study. The cohort study was performed at the Affiliated Jinhua Hospital of Wenzhou Medical University (Jinhua, China). A total of 31 women with adenomyosis were initially recruited from June 2020 to June 2022 and divided into an experimental group and a control group. The experimental group underwent hysteroscopic LNG-IUD fixation surgery and the control group underwent conventional implantation of the levonorgestrel-releasing intrauterine system. The assessed efficacy outcomes included the time of LNG-IUD expulsion, postoperative vaginal bleeding time, dysmenorrhea, and the menstrual blood loss score (MBLS). A total of 31 participants completed the research. The LNG-IUD expulsion rate was 6.25 and 60% (P<0.05) in the experimental and control group, respectively. The LNG-IUD in place time was 20.50 months (Q1, 15.75; Q3, 24.00) in the experimental group and 10.00 months (Q1, 6.50; Q3, 15.00) in the control group (P<0.05); the time of vaginal bleeding after surgery in the experimental and control groups were 12.50 days (9.25, 16.25) and 120.00 days (75.00, 120.00), respectively (P<0.05). Multiple-factor Cox regression analysis revealed that the LNG-IUD expulsion in patients with adenomyosis is associated with the hysteroscopic LNG-IUD fixation surgery [hazard ratio (HR), 1954.09], uterine cavity depth (HR, 16.63), MBLS (HR, 1.14), history of gonadotropin-releasing hormone agonist treatment in the previous 6 months (HR, 2.10), history of vaginal delivery (HR, 1.79) and history of cervical laceration (HR, 3.69). In conclusion, hysteroscopic LNG-IUD fixation reduces the rate of LNG-IUD expulsion, prolongs the time of LNG-IUD in the uterine cavity, reduces the time of postoperative vaginal bleeding, relieves the symptoms of dysmenorrhea and reduces the menstrual volume in the patients with adenomyosis. The present trial was retrospectively registered in the Chinese Clinical Trial Registry on 28th December 2023 (registration no. ChiCTR2300079233).

Inflammatory Markers Associated with Physical Frailty and Cognitive Impairment.

In older adults, physical frailty and cognitive impairment contribute to adverse outcomes. However, the research on mechanisms underlying physical frailty and cognitive impairment is limited. Low-grade chronic inflammation is a characteristic of aging. Particularly, an imbalance in pro- and anti-inflammatory mechanisms may be involved in frailty and neurodegenerative disorders. Therefore, exploring the inflammatory markers of physical frailty and cognitive impairment is crucial to fully understanding these mechanisms and establishing a substantial link between these two disorders. Notably, few studies have focused on exploring inflammatory markers in both physical frailty and cognitive impairment, posing a major challenge in elucidating the link between them. Therefore, substantial efforts are required for the better prevention of physical frailty and cognitive impairment. In this review, we explored the role of inflammatory markers as a potential link between frailty and cognitive impairment.

GhTKPR1_8 functions to inhibit anther dehiscence and reduce pollen viability in cotton.

Sporopollenin, as the main component of the pollen exine, is a highly resistant polymer that provides structural integrity under unfavourable environmental conditions. Tetraketone α-pyrone reductase 1 (TKPR1) is essential for sporopollenin formation, catalyzing the reduction of tetraketone carbonyl to hydroxylated α-pyrone. The functional role of TKPR1 in male sterility has been reported in flowering plants such as maize, rice, and Arabidopsis. However, the molecular cloning and functional characterization of TKPR1 in cotton remain unaddressed. In this study, we identified 68 TKPR1s from four cotton species, categorized into three clades. Transcriptomics and RT-qPCR demonstrated that GhTKPR1_8 exhibited typical expression patterns in the tetrad stage of the anther. GhTKPR1_8 was localized to the endoplasmic reticulum. Moreover, ABORTED MICROSPORES (GhAMS) transcriptionally activated GhTKPR1_8 as indicated by luciferase complementation tests. GhTKPR1_8-knockdown inhibited anther dehiscence and reduced pollen viability in cotton. Additionally, overexpression of GhTKPR1_8 in the attkpr1 mutant restored its male sterile phenotype. This study offers novel insights into the investigation of TKPR1 in cotton while providing genetic resources for studying male sterility.

AKR1B10 expression characteristics in hepatocellular carcinoma and its correlation with clinicopathological features and immune microenvironment.

Hepatocellular carcinoma (HCC) represents a major global health threat with diverse and complex pathogenesis. Aldo-keto reductase family 1 member B10 (AKR1B10), a tumor-associated enzyme, exhibits abnormal expression in various cancers. However, a comprehensive understanding of AKR1B10's role in HCC is lacking. This study aims to explore the expression characteristics of AKR1B10 in HCC and its correlation with clinicopathological features, survival prognosis, and tumor immune microenvironment, further investigating its role and potential regulatory mechanisms in HCC. This study conducted comprehensive analyses using various bioinformatics tools and databases. Initially, differentially expressed genes related to HCC were identified from the GEO database, and the expression of AKR1B10 in HCC and other cancers was compared using TIMER and GEPIA databases, with validation of its specificity in HCC tissue samples using the HPA database. Furthermore, the relationship of AKR1B10 expression with clinicopathological features (age, gender, tumor size, staging, etc.) of HCC patients was analyzed using the TCGA database's LIHC dataset. The impact of AKR1B10 expression levels on patient prognosis was evaluated using Kaplan-Meier survival analysis and the Cox proportional hazards model. Additionally, the correlation of AKR1B10 expression with tumor biology-related signaling pathways and tumor immune microenvironment was studied using databases like GSEA, Targetscan, and others, identifying microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate AKR1B10 expression to explore potential regulatory mechanisms. Elevated AKR1B10 expression was significantly associated with gender, primary tumor size, and fibrosis stage in HCC tissues. High AKR1B10 expression indicated poor prognosis and served as an independent predictor for patient outcomes. Detailed mechanism analysis revealed a positive correlation between high AKR1B10 expression, immune cell infiltration, and pro-inflammatory cytokines, suggesting a potential DANCR-miR-216a-5p-AKR1B10 axis regulating the tumor microenvironment and impacting HCC development and prognosis. The heightened expression of AKR1B10 in HCC is not only related to significant clinical-pathological traits but may also influence HCC progression and prognosis by activating key signaling pathways and altering the tumor immune microenvironment. These findings provide new insights into the role of AKR1B10 in HCC pathogenesis and highlight its potential as a biomarker and therapeutic target.

A sustainable carbon aerogel from waste paper with exceptional performance for antibiotics removal from water.

In this work, a sustainable 3D carbon aerogel (AO-WPC) is prepared from waste paper (WP), and used for efficient antibiotics removal from water. The AO-WPC aerogel shows good mechanical property and can recover after 100th of 30 % compression strain. The specific surface area of AO-WPC aerogel is up to 654.58 m2/g. More importantly, this aerogel reveals proper pore size distribution, including micro sized macropores between carbon fibers and intrinsic nano scale mesopores (11.86 nm), which is conducive to remove antibiotics from water. Taking tetracycline (Tc) as an example, the maximum adsorption capacity and adsorption rate of AO-WPC for Tc are as high as 384.6 mg/g and 0.510 g/(mg‧min), respectively, which exhibits significant advantages over most of the recent absorbents, and the adsorption toward Tc reveals good resistance to various environmental factors, including pH, various ions, and dissolved organic matter (DOM). Moreover, good thermal stability enables the AO-WPC aerogel to be regenerated through simple burning, and the adsorption capacity of Tc only decreases by 10.4 % after 10 cycles. Mechanism research shows that hydrogen bonding and π-π electron-donor-acceptor (EDA) interaction play the important role in the adsorption. The excellent mechanical property and adsorption performance imply good practical prospect of the AO-WPC aerogel.

Trajectory of intrinsic capacity among community-dwelling older adults in China: The China health and retirement longitudinal study.

BACKGROUNDS: Intrinsic capacity (IC), the sum of individual mental and physical capabilities, as well as living environment and behavior, jointly determine the functional ability of older adults, shifting the focus from disease to function. At the population level, IC in older adults is associated with adverse health outcomes, such as disability, falls, and death. At the individual level, IC changes dynamically. However, studies on the longitudinal IC trajectory and the factors influencing IC deterioration are limited. We aimed to analyze the IC trajectory and explore the risk factors for IC deterioration in Chinese older adults. METHODS: Data were obtained from the baseline (2011-2012) and 4-year follow-up (2015) CHARLS surveys, including 1906 people aged 60 years and older. IC comprises six dimensions: locomotion, vitality, hearing, vision, cognition, and psychology. IC trajectory was categorized into three groups: improved, maintained, and deteriorated. Logistic regression analysis was used to analyze factors influencing the trajectory of IC deterioration. RESULTS: After 4 years, 32.1 % had deteriorated, 38.5 % remained stable, and 29.4 % had improved. Age, low level of education, widowed were independently associated with IC deterioration. CONCLUSIONS: Dynamic IC monitoring supports the development of individualized intervention policies to delay or prevent IC deterioration.

Systematic identification and analysis of immune-related circRNAs of Pelteobagrus fulvidraco involved in Aeromonas veronii infection.

Circular RNA (circRNA) represents a type of newly discovered non-coding RNA, distinguished by its closed loop structure formed through covalent bonds. Recent studies have revealed that circRNAs have crucial influences on host anti-pathogen responses. Yellow catfish (Pelteobagrus fulvidraco), an important aquaculture fish with great economic value, is susceptible to Aeromonas veronii, a common aquatic pathogen that can cause acute death. Here, we reported the first systematic investigation of circRNAs in yellow catfish, especially those associated with A. veronii infection at different time points. A total of 1205 circRNAs were identified, which were generated from 875 parental genes. After infection, 47 circRNAs exhibited differential expression patterns (named DEcirs). The parental genes of these DEcirs were functionally engaged in immune-related processes. Accordingly, seven DEcirs (novel_circ_000226, 278, 401, 522, 736, 843, and 975) and six corresponding parental genes (ADAMTS13, HAMP1, ANG3, APOA1, FGB, and RALGPS1) associated with immunity were obtained, and their expression was confirmed by RT-qPCR. Moreover, we found that these DEcir-gene pairs likely acted through pathways, such as platelet activation, antimicrobial humoral response, and regulation of Ral protein signal transduction, to influence host immune defenses. Additionally, integrated analysis showed that, of the 7 immune-related DEcirs, three targeted 16 miRNAs, which intertwined into circRNA-miRNA networks. These findings revealed that circRNAs, by targeting genes or miRNAs are highly involved in anti-bacterial responses in yellow catfish. Our study comprehensively illustrates the roles of circRNAs in yellow catfish immune defenses. The identified DEcirs and the circRNA-miRNA network will contribute to the further investigations on the molecular mechanisms underlying yellow catfish immune responses.

Comparative Study of the Short-Term Efficacy and Safety between DEB-TACE and C-TACE in the Treatment of Unresectable Hepatocellular Carcinoma, a Retrospective Study.

Background: This is a retrospective study aimed at comparing the clinical efficacy and safety between drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) and conventional TACE (C-TACE) in the treatment of unresectable hepatocellular carcinoma. Methods: From July 2019 to April 2021, we enrolled 282 patients with unresectable hepatocellular carcinoma who were admitted to our hospital, of which 179 and 103 were in the DEB-TACE and C-TACE groups, respectively. General information was collected, and treatment effects were evaluated following the modified Response Evaluation Criteria in Solid Tumors. To compare the indexes of liver and kidney function, routine blood and coagulation were collected before treatment, and 1 day, 1 month, 3 months, and 6 months postoperatively. Postoperative adverse reactions (ie, fever, nausea, vomiting, anorexia, abdominal pain) were recorded to evaluate the safety of treatment. The two groups' progression-free survival and overall survival were also calculated to assess the treatment effect. Results: Preoperatively, the bilirubin, transaminase, and absolute neutrophil values between the two groups were not statistically significant (P > .05). At 1 month postoperatively, the absolute neutrophil values were significantly higher in the DEB-TACE group than those in the C-TACE group (P < .05). At 3 months postoperatively, AST, total bilirubin, and direct bilirubin levels were significantly elevated in the DEB-TACE group (P < .05), compared with the C-TACE group. However, at 6 months postoperatively, total and direct bilirubin levels in the C-TACE group were higher than those in the DEB-TACE group, showing a statistically significant difference (P < .05). For patients undergoing DEB-TACE, the survival risk was lower compared to those undergoing C-TACE. The survival risk of patients undergoing DEB-TACE was lower than that of C-TACE within 20 months postoperatively. The survival risk of patients undergoing DEB-TACE was lower than that of patients undergoing C-TACE. Conclusion: DEB-TACE may be superior to C-TACE in terms of safety and efficacy in the treatment of unresectable hepatocellular carcinoma.

Construction and Verification of Urinary Tract Infection Prediction Model for Hospitalized Rehabilitation Patients with Spinal Cord Injury.

OBJECTIVE: To explore the influencing factors of urinary tract infection (UTI) in hospitalized patients with spinal cord injury and to construct and verify the nomogram prediction model. METHODS: This study is a retrospective cohort study. From January 2017 to March 2022, 558 patients with spinal cord injury admitted to the Department of Rehabilitation Medicine of a tertiary hospital in Anhui Province, China, were selected as the research objects, and they were randomly divided into training group (n = 390) and verification group (n = 168) according to the ratio of 7:3, and clinical data including socio-demographic characteristics, disease-related data, and laboratory examination data were collected. Univariate analysis and multivariate logistic regression were used to analyze the influencing factors of UTI in hospitalized patients with spinal cord injuries. Based on this, a nomogram prediction model was constructed with the use of R software, and the risk prediction efficiency of the nomogram model was verified by the receiver operating characteristic curve and calibration curve. RESULTS: Logistic regression analysis showed that the American Spinal Cord Injury Association (ASIA)-E grade (compared with ASIA-A grade) was an independent protective factor for UTI in hospitalized patients with spinal cord injury (odds ratio < 1, P < 0.05), while white blood cell count and indwelling catheter were independent risk factors for UTI in hospitalized patients with spinal cord injury (odds ratio > 1, P < 0.05). Based on this, a nomogram risk predictive model for predicting UTI in hospitalized rehabilitation patients with spinal cord injury was constructed, which proved to have good predictive efficiency. In the training group and the verification group, the area under the receiver operating characteristic curve of the nomogram model is 0.808 and 0.767, and the 95% confidence interval of the area under the receiver operating characteristic curve of the nomogram in the training group and the verification group is 0.760∼0.856 and 0.688∼0.845, respectively, indicating the nomogram model has good discrimination. According to the calibration curve, the prediction probability of the nomogram model and the actual frequency of UTI in the training group and the verification group are in good consistency, and the results of the Hosmer-Lemeshow bias test also suggest that the nomogram model has a good calibration degree in both the training group and the verification group (P = 0.329, 0.067). CONCLUSIONS: ASIA classification level, white blood cell count, and indwelling catheter are independent influencing factors of UTI in hospitalized patients with spinal cord injury. The nomogram prediction model based on the above factors can simply and effectively predict the risk of UTI in hospitalized patients with spinal cord injury, which is helpful for clinical medical staff to identify high-risk groups early and implement prevention, treatment, and nursing strategies in time.