Construction of nomogram based on clinical factors for the risk prediction of postoperative complications in children with choledochal cyst.

Objective: The aim of the study was to develop a prediction nomogram based on clinical factors to assess the risk of postoperative complications in children with congenital choledochal cyst. Methods: The clinical data from 131 children who underwent choledochal cyst resection and Roux-en-Y hepaticojejunostomy in our hospital between January 2016 and December 2022 were retrospectively analyzed. The general information, clinical symptoms, procedure, biochemical indicators, and imaging data were recorded. A prolonged hospital stay induced by postoperative complications or a follow-up over 6 months was assessed as the event outcome. A logistics regression analysis was performed to screen for risk factors with statistical significance in inducing postoperative complications. Then, with the dataset split into the training group and internal validation group, the nomogram for the prediction of postoperative complications was developed based on a computer algorithm. In addition, the receiver operating characteristic (ROC) curve and calibration curve were performed for nomogram verification. Results: Of 131 children, the multivariate logistics regression analysis suggested that age ≤2 years [odds ratio (OR) 0.93; 95% confidence interval (CI) 0.15-5.65; p = 0.938], Todani classification type 1 (OR 36.58; 95% CI 4.14-871.74; p = 0.005), cyst wall thickness >0.4 cm (OR 10.82; 95% CI 2.88-49.13; p < 0.001), with chronic cholecystitis (OR 7.01; 95% CI 1.62-38.52; p = 0.014), and choledochal cyst diameter (OR 1.01; 95% CI 0.99-1.03; p = 0.370) were predictors associated with the postoperative complications of choledochal cysts. The data were randomly divided into the training group (n = 92) and internal validation group (n = 39) to build the prediction nomogram including the appeal factors. The accuracy and discrimination of the model were evaluated using a ROC curve and calibration curve. The results showed that the nomogram area under the ROC curve [area under the curve (AUC) = 0.894; 95% CI 0.822-0.966; p < 0.001], validation (AUC = 0.844; 95% CI 0.804-0.952; p < 0.001), and Brier = 0.120 (95% CI 0.077-0.163p; p < 0.001) were indicative of the good stability and calibration of the predictive nomogram. Conclusion: The prognosis of congenital choledochal cysts was associated with multiple aspects of clinical factors. Combined with the internal validation, the novel prediction nomogram was suitable for evaluating the individualized risk of postoperative complications of choledochal cysts. The prediction nomogram could provide a more accurate strategy of procedure and postoperative follow-up for children with choledochal cysts.

Dynamics of Physiological Properties and Endophytic Fungal Communities in the Xylem of Aquilaria sinensis (Lour.) with Different Induction Times.

Xylem-associated fungus can secrete many secondary metabolites to help Aquilaria trees resist various stresses and play a crucial role in facilitating agarwood formation. However, the dynamics of endophytic fungi in Aquilaria sinensis xylem after artificial induction have not been fully elaborated. Endophytic fungi communities and xylem physio-biochemical properties were examined before and after induction with an inorganic salt solution, including four different times (pre-induction (0M), the third (3M), sixth (6M) and ninth (9M) month after induction treatment). The relationships between fungal diversity and physio-biochemical indices were evaluated. The results showed that superoxide dismutase (SOD) and peroxidase (POD) activities, malondialdehyde (MDA) and soluble sugar content first increased and then decreased with induction time, while starch was heavily consumed after induction treatment. Endophytic fungal diversity was significantly lower after induction treatment than before, but the species richness was promoted. Fungal ß-diversity was also clustered into four groups according to different times. Core species shifted from rare to dominant taxa with induction time, and growing species interactions in the network indicate a gradual complication of fungal community structure. Endophytic fungi diversity and potential functions were closely related to physicochemical indices that had less effect on the relative abundance of the dominant species. These findings help assess the regulatory mechanisms of microorganisms that expedite agarwood formation after artificial induction.

Microfluidics in smart food safety.

The evolution of food safety practices is crucial in addressing the challenges posed by a growing global population and increasingly complex food supply chains. Traditional methods are often labor-intensive, time-consuming, and susceptible to human error. This chapter explores the transformative potential of integrating microfluidics into smart food safety protocols. Microfluidics, involving the manipulation of small fluid volumes within microscale channels, offers a sophisticated platform for developing miniaturized devices capable of complex tasks. Combined with sensors, actuators, big data analytics, artificial intelligence, and the Internet of Things, smart microfluidic systems enable real-time data acquisition, analysis, and decision-making. These systems enhance control, automation, and adaptability, making them ideal for detecting contaminants, pathogens, and chemical residues in food products. The chapter covers the fundamentals of microfluidics, its integration with smart technologies, and its applications in food safety, addressing the challenges and future directions in this field.

Identifying Acute Aortic Syndrome and Thoracic Aortic Aneurysm from Chest Radiography in the Emergency Department Using Convolutional Neural Network Models.

(1) Background: Identifying acute aortic syndrome (AAS) and thoracic aortic aneurysm (TAA) in busy emergency departments (EDs) is crucial due to their life-threatening nature, necessitating timely and accurate diagnosis. (2) Methods: This retrospective case-control study was conducted in the ED of three hospitals. Adult patients visiting the ED between 1 January 2010 and 1 January 2020 with a chief complaint of chest or back pain were enrolled in the study. The collected chest radiography (CXRs) data were divided into training (80%) and testing (20%) datasets. The training dataset was trained by four different convolutional neural network (CNN) models. (3) Results: A total of 1625 patients were enrolled in this study. The InceptionV3 model achieved the highest F1 score of 0.76. (4) Conclusions: Analysis of CXRs using a CNN-based model provides a novel tool for clinicians to interpret ED patients with chest pain and suspected AAS and TAA. The integration of such imaging tools into ED could be considered in the future to enhance the diagnostic workflow for clinically fatal diseases.

Predictive value of Vitamin D levels in pregnant women on gestational length and neonatal weight in China: a population-based retrospective study.

BACKGROUND: Vitamin D deficiency, a common occurrence among pregnant women, is an emerging public health concern worldwide. According to research, prenatal vitamin D deficiency is associated with various complications. This study assessed the vitamin D status of pregnant women in Yanbian, Jilin Province, as well as the correlation and predictive value of their vitamin D levels in relation to gestational length (weeks) and fetal weight, aiming to provide a basis for clinical diagnosis and treatment. METHODS: We conducted a population-based retrospective study involving 510 pregnant women from August 2019 to October 2022. Blood samples were collected at 16-20 weeks of gestation for the detection of serum vitamin D levels. Statistical analyses were performed using SPSS 28.0 and R 4.1.0 software. Multifactorial logistic regression analysis was employed to establish whether each variable was a risk factor for deliveries at ≤ 38 gestational weeks and low fetal weight. These results were used to construct a risk prediction model, and the model's predictive efficacy was evaluated. Results or differences with p < 0.05 were considered statistically significant. RESULTS: Multifactorial logistic regression analysis revealed that vitamin D ≤ 14.7 ng/mL(OR: 1.611; 95% CI: 1.120-2.318; P = 0.010), Bone Mineral Density (BMD) T-value ≤-1(OR: 1.540; 95%CI: 1.067-2.223; P = 0.021), and gestational hypertension(OR: 7.173; 95% CI: 1.482-34.724; P = 0.014) were the independent risk factors for deliveries at ≤ 38 gestational weeks. Additionally, vitamin D ≤ 14.7 ng/mL(OR: 1.610; 95%CI: 1.123-2.307; P = 0.009), BMD T-value ≤ -1(OR: 1.560; 95%CI: 1.085-2.243; P = 0.016), and gestational hypertension(OR: 4.262; 95% CI: 1.058-17.167; P = 0.041) were the independent risk factors for low fetal weight (< 3400 g). CONCLUSION: This study revealed that low vitamin D levels are an independent risk factor for a short gestational length and low fetal weight. Prenatal low BMD T-value and comorbid hypertensive disorders were also found to increase the risk of a short gestational length and low fetal weight.

Seven-Day Vonoprazan-Based Triple Therapy as First-Line Helicobacter pylori Treatment in Comparison With Extended Sequential Therapy: A Randomized Controlled Trial.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, has demonstrated greater potency and a longer duration of acid suppression when compared to the proton pump inhibitors. However, data regarding the comparison between vonoprazan-based triple therapy with standard treatment for first-line Helicobacter pylori treatment are limited. This study aimed to compare the efficacy between 7-day vonoprazan-based triple therapy with high-dose amoxicillin (VAC-7) and 14-day extended sequential therapy (S-14). MATERIALS AND METHODS: This was a single-center prospective randomized controlled trial following a noninferiority design. Subjects over 20 years old with confirmed H. pylori infection were enrolled prospectively from Fu Jen Catholic University Hospital. They were randomly assigned to the VAC-7 or S-14 group. The primary endpoint was the eradication rate in first-line treatment, evaluated by urea breath test, with noninferiority determined using the Farrington-Manning method. The secondary outcome included adverse effect rates and compliance, assessed through self-administered questionnaires. RESULTS: Between December 2021 and June 2023, a total of 628 patients were recruited. The eradication rates by per-protocol analysis and intention-to-treat analysis were 88.6%/81.8% for VAC-7 and 90.3%/81.4% for S-14, respectively. The VAC-7 was non-inferior to S-14 in terms of ITT analysis. Subjects experienced fewer incidences of nausea, anorexia, dizziness, fatigue, and any severe adverse events in the VAC-7 group. Compliance was higher in the VAC-7 group, with 94% taking all the pills correctly. CONCLUSIONS: Our findings supported the use of 7-day vonoprazan triple therapy with high-dose amoxicillin as the standard first-line treatment for H. pylori infection. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05371249.

Ubiquitination and degradation of plant helper NLR by the Ralstonia solanacearum effector RipV2 overcome tomato bacterial wilt resistance.

The Ralstonia solanacearum species complex causes bacterial wilt in a variety of crops. Tomato cultivar Hawaii 7996 is a widely used resistance resource; however, the resistance is evaded by virulent strains, with the underlying mechanisms still unknown. Here, we report that the phylotype Ⅱ strain ES5-1 can overcome Hawaii 7996 resistance. RipV2, a type Ⅲ effector specific to phylotype Ⅱ strains, is vital in overcoming tomato resistance. RipV2, which encodes an E3 ubiquitin ligase, suppresses immune responses and Toll/interleukin-1 receptor/resistance nucleotide-binding/leucine-rich repeat (NLR) (TNL)-mediated cell death. Tomato helper NLR N requirement gene 1 (NRG1), enhanced disease susceptibility 1 (EDS1), and senescence-associated gene 101b (SAG101b) are identified as RipV2 target proteins. RipV2 is essential for ES5-1 virulence in Hawaii 7996 but not in SlNRG1-silenced tomato, demonstrating SlNRG1 to be an RipV2 virulence target. Our results dissect the mechanisms of RipV2 in disrupting immunity and highlight the importance of converged immune components in conferring bacterial wilt resistance.

CCL16 is a pro-tumor chemokine that recruits monocytes and macrophages to promote hepatocellular carcinoma progression.

Intricate signaling cascades involving chemokines and their cognate receptors on neoplastic and immune constituents within tumor microenvironment have garnered substantial research interest. Our investigation delineates the contribution of Chemokine (C-C motif) ligand 16 (CCL16) to the clinico-pathological features and tumorigenesis of hepatocellular carcinoma (HCC). Analysis of 237 pairs of HCC specimens unraveled a significant association between CCL16 expression and vascular invasion, early-stage clinicopathological features, and diminished recurrence-free survival among HCC patients. Immunohistochemical (IHC) assays of the clinical HCC specimens indicated elevated CCL16 in tumorous versus normal hepatic tissues. Our in vivo experiments demonstrated CCL16 overexpression fostered tumor proliferation, whereas in vitro assays elucidated that CCL16-mediated chemotactic recruitment of monocytes and M2 macrophages was orchestrated via CCR1 and CCR5. In contrast to previous claims that CCL16 is physiologically irrelevant and has minimal affinity for its receptors (CCR1, CCR2, CCR5, CCR8), our findings unravel that inhibition of CCL16/CCR1 and CCL16/CCR5 interactions through receptor-specific antagonists markedly impeded CCL16-directed chemotaxis, migration, adhesion, and leukocyte recruitment. Moreover, CCL16-overexpression in HCCs significantly augmented levels of several cytokines implicated in tumor progression, namely IL-6, IL-10 and VEGFA. IHC analysis of CCL16-overexpressing xenografts elicited greatly enhanced levels of VEGFA and IL-6, while assessments of HCC specimens confirmed a positive correlation between CCL16 expression and IL-6 and VEGFA levels. Collectively, our study highlights oncogenic role of CCL16 in hepatocarcinogenesis and provides a foundational basis for novel therapeutic interventions targeting the CCL16/CCR1/CCR5 axis.

Effects of Shoulder Corrective Training Program on Pitching Loads and Sonographic Morphology in Elbow Joint in Youth Baseball Players.

ABSTRACT: Chen, P-T, Lin, Y-C, Chang, H-Y, Chiu, C-H, Chen, C-Y, Chen, P, and Lin, Y-H. Effects of shoulder corrective training program on pitching loads and sonographic morphology in elbow joint in youth baseball players. J Strength Cond Res 38(8): e440-e447, 2024-We assessed the effects of a 12-week shoulder corrective training program for shoulder flexibility and strengthening on pitching loads and sonographic morphology of the elbow joints in youth baseball players. Seventeen subjects were recruited and underwent evaluations before and after the training program. We found that following training, subjects demonstrated significantly increased ranges of shoulder internal rotation (38.9 ± 12.9° vs. 69.2 ± 10.8°, p < 0.001), external rotation (91.2 ± 14.6° vs. 107.3 ± 9.5°, p = 0.004), and horizontal adduction (21.5 ± 8.0° vs. 32.7 ± 7.3°, p = 0.002); improved strength in the shoulder internal rotators (8.7 ± 1.6 kg vs. 9.8 ± 2.1 kg, p = 0.04), external rotators (6.5 ± 1.9 kg vs. 7.5 ± 2.8 kg, p = 0.04), middle trapezius (12.7 ± 2.1 kg vs. 14.3 ± 2.4 kg, p = 0.04), and middle deltoid muscles (10.8 ± 3.3 kg vs. 14.8 ± 3.2 kg, p = 0.001); and decreased thickness of the ulnar collateral ligament (6.1 ± 0.6 mm vs. 4.8 ± 0.7 mm, p = 0.002). Although there was no substantial change in elbow torque and arm speed, significantly increased ball speed (51.2 ± 4.6 mph vs. 54.1 ± 4.5 mph, p < 0.001) and decreased arm slot (63.8 ± 11.9° vs. 53.0 ± 12.7°, p = 0.02) were observed. We suggest that adequate corrective training should be performed regularly to minimize or mitigate adverse soft tissue changes at the elbow in youth baseball players. Balanced shoulder strength and flexibility may decrease medial elbow stress during pitching. Future studies should consider the kinetic and kinematic effects of other corrective training programs on the shoulder or elbow joint during pitching.

Hypericum perforatum L. attenuates depression by regulating Akkermansia muciniphila, tryptophan metabolism and NFκB-NLRP2-Caspase1-IL1ß pathway.

BACKGROUND: Gut microbiota dysbiosis significantly contributes to progression of depression. Hypericum perforatum L. (HPL) is traditionally used in Europe for treating depression. However, its mechanism remains largely underexplored. PURPOSE: This study aims to investigate the pivotal gut microbiota species and microbial signaling metabolites associated with the antidepressant effects of HPL. METHODS: Fecal microbiota transplantation was used to assess whether HPL mitigates depression through alterations in gut microbiota. Microbiota and metabolic profiling of control, chronic restraint stress (CRS)-induced depression, and HPL-treated CRS mice were examined using 16S rRNA gene sequencing and metabolomics analysis. The influence of gut microbiota on HPL's antidepressant effects was assessed by metabolite and bacterial intervention experiments. RESULTS: HPL significantly alleviated depression symptoms in a manner dependent on gut microbiota and restored gut microbial composition by enriching Akkermansia muciniphila (AKK). Metabolomic analysis indicated that HPL regulated tryptophan metabolism, reducing kynurenine (KYN) levels derived from microbiota and increasing 5-hydroxytryptophan (5-HTP) levels. Notably, supplementation with KYN activated the NFκB-NLRP2-Caspase1-IL1ß pathway and increased proinflammatory IL1ß in the hippocampus of mice with depression. Interestingly, mono-colonization with AKK notably increased 5-hydroxytryptamine (5-HT) and decreased KYN levels, ameliorating depression symptoms through modulation of the NFκB-NLRP2-Caspase1-IL1ß pathway. CONCLUSIONS: The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NFκB-NLRP2-Caspase1-IL1ß pathway, specifically by targeting AKK and tryptophan metabolites.

Deferoxamine alleviates chondrocyte senescence and osteoarthritis progression by maintaining iron homeostasis.

BACKGROUND: Osteoarthritis (OA) is a prevalent age-related disease characterized by the gradual deterioration of cartilage. The involvement of chondrocyte senescence is crucial in the pathogenesis of OA. Desferoxamine (DFO) is an iron chelator with therapeutic potential in various diseases. However, the relationship of chondrocyte senescence and iron homeostasis is largely unknown. METHODS: Chondrocyte senescence was induced using tert-butyl hydroperoxide (TBHP), and the impact of DFO on chondrocyte senescence and iron metabolism was assessed through techniques such as western blotting, qRT-PCR, and ß-Galactosidase staining. To assess the impact of DFO on chondrocyte senescence and the progression of osteoarthritis (OA), the surgical destabilization of the medial meniscus model was established. RESULTS: In chondrocytes, TBHP administration resulted in elevated expression of P16, P21, and P53, as well as alterations in SA-ß-gal staining. Nevertheless, DFO effectively mitigated chondrocyte senescence induced by TBHP, and reversed the decrease in collagen II expression and increase in MMP13 expression caused by TBHP. Mechanismly, TBHP induced NCOA4 expression and iron release in chondrocytes. Excessive iron could induce chondrocyte senescence, whereas, DFO could inhibit NCOA4 expression and restore ferritin level, and chelate excessive iron. Importantly, intra-articular injection of DFO enhanced collagen II expression and reduced expression of P16, P21, and MMP13 of cartilage in OA mice, and delayed cartilage degeneration. CONCLUSIONS: Overall, this study provides evidence that DFO has the potential to alleviate chondrocyte senescence induced by TBHP and slow down the progression of osteoarthritis (OA) by effectively chelating excessive iron. These findings suggest that iron chelation could be a promising therapeutic strategy for treating OA.

An Overview of Nanoparticle-Based Delivery Platforms for mRNA Vaccines for Treating Cancer.

With its unique properties and potential applications, nanoparticle-based delivery platforms for messenger RNA (mRNA) vaccines have gained significant attention in recent years. Nanoparticles have the advantages of enhancing immunogenicity, targeting delivery, and improving stability, providing a new solution for drug and vaccine delivery. In some clinical studies, a variety of nanoparticle delivery platforms have been gradually applied to a wide range of vaccine applications. Current research priorities are exploring various types of nanoparticles as vaccine delivery systems to enhance vaccine stability and immunogenicity. Lipid nanoparticles (LNPs) have shown promising potential in preclinical and clinical studies on the efficient delivery of antigens to immune cells. Moreover, lipid nanoparticles and other nanoparticles for nucleic acids, especially for mRNA delivery systems, have shown vast potential for vaccine development. In this review, we present various vaccine platforms with an emphasis on nanoparticles as mRNA vaccine delivery vehicles. We describe several novel nanoparticle delivery platforms for mRNA vaccines, such as lipid-, polymer-, and protein-based nanoparticles. In addition, we provide an overview of the anti-tumor immunity of nanovaccines against different tumors in cancer immunotherapy. Finally, we outline future perspectives and remaining challenges for this promising technology of nanoparticle-based delivery platforms for vaccines.

Characterization and Therapeutic Potential of Curcumin-Loaded Cerium Oxide Nanoparticles for Interstitial Cystitis Management.

Oxidative stress resulting from reactive oxygen species (ROS) is often considered to be the leading cause of interstitial cystitis (IC), which is a chronic inflammatory disease. Antioxidants have been proven to have promising therapeutic effects on IC. In this study, we present an antioxidant intervention for IC by introducing curcumin-loaded cerium oxide nanoparticles (Cur-CONPs). Recognizing oxidative stress as the primary contributor to IC, our research builds on previous work utilizing cerium oxide nanoparticles (CONPs) for their outstanding antioxidant and anti-inflammatory properties. However, given the need to effectively relieve acute inflammation, we engineered Cur-CONPs to harness the short-term radical-scavenging antioxidant prowess of curcumin. Through in vitro studies, we demonstrate that the Cur-CONPs exhibit not only robust antioxidant capabilities but also superior anti-inflammatory properties over CONPs alone. Furthermore, in vivo studies validate the therapeutic effects of Cur-CONPs on IC. Mice with IC subjected to the Cur-CONP treatment exhibited improved micturition behaviors, relief from pelvic pain sensitivity, and reduced expression of inflammatory proteins (IL-6, IL-1ß, TNF-α, Cox2). These findings suggest that the synergistic antioxidant properties of the Cur-CONPs that combine the sustained antioxidant properties of CONPs and acute anti-inflammatory capabilities of curcumin hold promise as a novel treatment strategy for IC.

Multi-Omics Characterization of E3 Regulatory Patterns in Different Cancer Types.

Ubiquitination, a post-translational modification, refers to the covalent attachment of ubiquitin molecules to substrates. This modification plays a critical role in diverse cellular processes such as protein degradation. The specificity of ubiquitination for substrates is regulated by E3 ubiquitin ligases. Dysregulation of ubiquitination has been associated with numerous diseases, including cancers. In our study, we first investigated the protein expression patterns of E3 ligases across 12 cancer types. Our findings indicated that E3 ligases tend to be up-regulated and exhibit reduced tissue specificity in tumors. Moreover, the correlation of protein expression between E3 ligases and substrates demonstrated significant changes in cancers, suggesting that E3-substrate specificity alters in tumors compared to normal tissues. By integrating transcriptome, proteome, and ubiquitylome data, we further characterized the E3-substrate regulatory patterns in lung squamous cell carcinoma. Our analysis revealed that the upregulation of the SKP2 E3 ligase leads to excessive degradation of BRCA2, potentially promoting tumor cell proliferation and metastasis. Furthermore, the upregulation of E3 ubiquitin-protein ligase TRIM33 was identified as a biomarker associated with a favorable prognosis by inhibiting the cell cycle. This work exemplifies how leveraging multi-omics data to analyze E3 ligases across various cancers can unveil prognosis biomarkers and facilitate the identification of potential drug targets for cancer therapy.

Combined Electrochemical Deposition and Photo-Reduction to Fabricate SERS-Active Silver Substrates: Characterization and Application for Malachite Green Detection in Aquaculture Water.

This research introduces a novel approach using silver (Ag) nanostructures generated through electrochemical deposition and photo-reduction of Ag on fluorine-doped tin oxide glass substrates (denoted as X-Ag-AgyFTO, where 'X' and 'y' represent the type of light source and number of deposited cycles, respectively) for surface-enhanced Raman spectroscopy (SERS). This study used malachite green (MG) as a Raman probe to evaluate the enhancement factors (EFs) in SERS-active substrates under varied fabrication conditions. For the substrates produced via electrochemical deposition, we determined a Raman EF of 6.15 × 104 for the Ag2FTO substrate. In photo-reduction, the impact of reductant concentration, light source, and light exposure duration were examined on X-Ag nanoparticle formation to achieve superior Raman EFs. Under optimal conditions (9.0 mM sodium citrate, 460 nm blue-LED at 10 W for 90 min), the combination of blue-LED-reduced Ag (B-Ag) and an Ag2FTO substrate (denoted as B-Ag-Ag2FTO) exhibited the best Raman EF of 2.79 × 105. This substrate enabled MG detection within a linear range of 0.1 to 1.0 µM (R2 = 0.98) and a detection limit of 0.02 µM. Additionally, the spiked recoveries in aquaculture water samples were between 90.0% and 110.0%, with relative standard deviations between 3.9% and 6.3%, indicating the substrate's potential for fungicide detection in aquaculture.

DrugRepoBank: a comprehensive database and discovery platform for accelerating drug repositioning.

In recent years, drug repositioning has emerged as a promising alternative to the time-consuming, expensive and risky process of developing new drugs for diseases. However, the current database for drug repositioning faces several issues, including insufficient data volume, restricted data types, algorithm inaccuracies resulting from the neglect of multidimensional or heterogeneous data, a lack of systematic organization of literature data associated with drug repositioning, limited analytical capabilities and user-unfriendly webpage interfaces. Hence, we have established the first all-encompassing database called DrugRepoBank, consisting of two main modules: the 'Literature' module and the 'Prediction' module. The 'Literature' module serves as the largest repository of literature-supported drug repositioning data with experimental evidence, encompassing 169 repositioned drugs from 134 articles from 1 January 2000 to 1 July 2023. The 'Prediction' module employs 18 efficient algorithms, including similarity-based, artificial-intelligence-based, signature-based and network-based methods to predict repositioned drug candidates. The DrugRepoBank features an interactive and user-friendly web interface and offers comprehensive functionalities such as bioinformatics analysis of disease signatures. When users provide information about a drug, target or disease of interest, DrugRepoBank offers new indications and targets for the drug, proposes new drugs that bind to the target or suggests potential drugs for the queried disease. Additionally, it provides basic information about drugs, targets or diseases, along with supporting literature. We utilize three case studies to demonstrate the feasibility and effectiveness of predictively repositioned drugs within DrugRepoBank. The establishment of the DrugRepoBank database will significantly accelerate the pace of drug repositioning. Database URL:  https://awi.cuhk.edu.cn/DrugRepoBank.

Trends in reported outcomes and patient reported outcome measures (PROMs) in humeral shaft fracture literature: a systematic review.

PURPOSE: With a lack of standardization among outcome measures in fracture literature, cross-study comparisons remain limited. This systematic review aimed to identify trends in outcome measures reported by studies of the treatment of humeral shaft fractures. METHODS: A systematic review was performed of studies reporting clinical outcomes of humeral shaft fractures indexed in PubMed. Extracted data included demographics, fracture characteristics, treatment modalities, outcomes, patient reported outcome measures (PROMs), and journal characteristics. Cochran-Armitage tests and linear regressions were used to identify data trends. Pearson chi-square and Kruskal-Wallis tests were used for comparisons between studies. RESULTS: This review included 197 studies with outcomes of 15,445 humeral shaft fractures. 126 studies reported PROMs and 37 different PROMs were used. The Constant Score was most commonly reported (34% of studies), followed by ASES Score (21%), MEPS (21%), and DASH Score (20%). There was a significant increase in PROM usage over time (p = 0.016) and in articles using three or more PROMs (p = 0.005). The number of PROMs were significantly greater in prospective cohort studies and RCTs (p = 0.012) compared to retrospective cohort studies and case series (p = 0.044 for both). Post-treatment shoulder motion was reported in 43% of studies and 34% reported elbow motion. 86% of studies reported complications as an outcome parameter. Time to union and nonunion rate were published in 69% and 88% of studies, respectively. CONCLUSION: This study identified increasing PROM usage over time and disparities in the reporting of outcomes in humeral shaft fracture literature requiring further validation and standardization of available outcome measures.

A trans-umbilical single-site plus one robotic-assisted surgery for choledochal cyst resection in children.

Objective: The purpose of this study is to compare the intraoperative and postoperative outcomes of a trans-umbilical single-site plus one robot-assisted surgery and a trans-umbilical single-site laparoscopic surgery in the treatment of choledochal cysts. Methods: We retrospectively analyzed clinical data from 49 children diagnosed with choledochal cysts who were admitted to our hospital between June 2020 and December 2023. Among these patients, 24 underwent a trans-umbilical single-site plus one Da Vinci robot-assisted surgery (the robot group) and 25 underwent a trans-umbilical single-site laparoscopic-assisted surgery (the laparoscopic group). We compared differences in intraoperative and postoperative outcomes between the two groups. Results: There was no significant difference between the two groups of patients in terms of gender, age, weight, clinical symptoms, maximum cyst diameter, type, postoperative complications, and facial expression, leg movement, activity, crying, and comfortability (FLACC) scoring (p > 0.05). Compared with the patients in the laparoscopic group, those in the robot group had less intraoperative bleeding [10 (8-12) vs. 15 (11.5-18) ml, p < 0.001] and required less postoperative drainage tube indwelling time [5 (4-6) vs. 7 (5.5-8) day, p < 0.001], less postoperative fasting time [4 (3-4) vs. 6 (5-7) days, p < 0.001], and less postoperative hospitalization time [6 (6-7) vs. 8 (6-10) days, p < 0.001], but they required more operative time [385.5 (317.0-413.3) vs. 346.0 (287.0-376.5) min, p = 0.050] and consumed more hospitalization expenses (79,323 ± 3,124 vs. 31,121 ± 2,918 yuan, p < 0.001). Conclusion: The results of this study showed a shorter hospitalization time, quicker postoperative recovery, and less tissue damage but a higher cost and a longer operation time in patients who chose robotic surgery rather than laparoscopic surgery. With the continuous expansion of the scale of installed robot-assisted surgical systems and the gradual accumulation of the technical experience of surgeons, robot-assisted surgery may slowly surpass, and shows a trend to replace, laparoscopy because of its advantages.

Investigating the Genetic Diversity of Hepatitis Delta Virus in Hepatocellular Carcinoma (HCC): Impact on Viral Evolution and Oncogenesis in HCC.

Hepatitis delta virus (HDV), an RNA virus with two forms of the delta antigen (HDAg), relies on hepatitis B virus (HBV) for envelope proteins essential for hepatocyte entry. Hepatocellular carcinoma (HCC) ranks third in global cancer deaths, yet HDV's involvement remains uncertain. Among 300 HBV-associated HCC serum samples from Taiwan's National Health Research Institutes, 2.7% (8/300) tested anti-HDV positive, with 62.7% (5/8) of these also HDV RNA positive. Genotyping revealed HDV-2 in one sample, HDV-4 in two, and two samples showed mixed HDV-2/HDV-4 infection with RNA recombination. A mixed-genotype infection revealed novel mutations at the polyadenylation signal, coinciding with the ochre termination codon for the L-HDAg. To delve deeper into the possible oncogenic properties of HDV-2, the predominant genotype in Taiwan, which was previously thought to be less associated with severe disease outcomes, an HDV-2 cDNA clone was isolated from HCC for study. It demonstrated a replication level reaching up to 74% of that observed for a widely used HDV-1 strain in transfected cultured cells. Surprisingly, both forms of HDV-2 HDAg promoted cell migration and invasion, affecting the rearrangement of actin cytoskeleton and the expression of epithelial-mesenchymal transition markers. In summary, this study underscores the prevalence of HDV-2, HDV-4, and their mixed infections in HCC, highlighting the genetic diversity in HCC as well as the potential role of both forms of the HDAg in HCC oncogenesis.