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ABSTRACT: Background: Osteosarcoma is the most common primary bone tumor in children. While the humerus is the third most common anatomic location, it is the most common site for fractures. Our objective is to characterize magnetic resonance imaging (MRI) features of humerus osteosarcoma in children and with respect to risk of sustaining a pathologic fracture. Methods: Children with histologically confirmed humerus osteosarcoma, who underwent preoperative MRI (2008-2023) were included. Two radiologists retrospectively reviewed all MRIs to determine medullary (skip lesions and trans-epiphyseal tumor), joint, and extraosseous (muscle, neurovasculature, and lymphadenopathy) disease. Tumor volumes were measured at diagnosis and after neoadjuvant chemotherapy, and findings between those with and without fractures were compared. Results: This study included 25 children (10 boys, 15 girls; mean age: 12.9 ± 4.2 years), 9 (36%) with (6 at diagnosis, 3 during treatment) and 16 (64%) without fractures. Radiologists’ agreement on various MRI characteristics including bone, joint, muscle, and neurovascular involvement of humerus osteosarcoma ranged between 60 and 100%. The most common findings included trans-epiphyseal tumor (80%), involvement of the long head of the biceps tendon (76%), and axillary neurovasculature (72%). Although tumor volumes were smaller in patients with (104 cm3, interquartile range [IQR]: 68-116) than without fractures (136 cm3, IQR: 100-216), this difference did not reach significance (p = .07); no other findings differed between the groups (p > .05). At a median follow-up of 17 months (IQR: 7-55), 52% relapsed, but no significant association was found between relapse and fracture (p = .69). Conclusions: Over a third of the patients with humerus osteosarcoma had pathologic fractures in our study group, but these did not significantly associate with larger tumor size, specific MRI features, or increased risk for disease relapse. Key Concepts: (1) The most common MRI findings in children with humerus osteosarcoma were trans-epiphyseal disease, followed by extraosseous disease involving the long head of the biceps tendon and the axillary neurovasculature. (2) The lack of significant differences between fracture and nonfracture groups in terms of serum biomarkers, histologic subtype and treatment response, MRI findings and outcome suggest that these fractures may result from a combination of tumor-related and patient-specific factors, but do not significantly associate with increased risk for relapse. Level of Evidence: III, retrospective cohort study

Background: Discoid lateral meniscus (DLM) is the most common congenital abnormality of the meniscus. Tears are common; treatment is frequently not definitive, often requiring reoperation. Purpose: To report the clinical manifestations, physical characteristics, operative treatments and findings, complications, and reoperations of DLM in pediatric patients from multiple centers across North America. Study Design: Case series; Level of evidence, 4. Methods: Consecutive patients who underwent treatment for symptomatic DLM at 9 institutions between 2000 and 2020 were included. Patient data, presenting symptoms and signs, surgical findings, treatments rendered, and postoperative complications, including reoperation rates, were collected. Means with ranges and counts with proportions are reported for continuous and categorical variables, respectively, and comparisons were made using either the chi-square or Fisher exact test. Results: In total, 784 patients (867 knees) were included with a mean age at diagnosis of 12 years (range, 1-22 years) and a mean follow-up of 22.6 months (range, 0-154 months). Common preoperative symptoms were locking (33%) and snapping (30%). At surgery, tears in the DLM were present in 647 knees (594 patients [76%]); 95 knees (11%) had multiple tears; and in 140 knees, tears extended into >1 zone. Tears, when present, were more common within the posterior horn (41%) or body (34%) than the anterior horn (25%). Peripheral rim instability was reported in 241 knees (28%). Significantly more knees had instability posteriorly (15%; P =.0004) and anteriorly (9%; P =.0013) than along the body (3%). Tear type was most commonly complex (38%) or horizontal (34%). A total of 358 knees in 333 patients with tears (42% of all patients) underwent repair (55% of knees with tears). A total of 175 complications were reported, occurring in 139 knees in 134 patients (17%); 116 of these knees with complications (83%) had a single complication, while 23 (17%) had >1. Of the 784 patients, 105 (13%) underwent reoperation, undergoing 135 additional procedures related to their DLM. Of those, 60 (44%) were repeat arthroscopy and meniscal trim; 40 (30%), arthroscopy and meniscal repair; and 17 (13%), an articular cartilage procedure. Conclusion: Locking and snapping were common presenting symptoms. Over three-quarters of patients had meniscal tears, which were most often complex and located posteriorly. Seventeen percent of patients experienced complications, and a sixth of patients with complications had >1. Reoperation was typically for persistent symptoms or meniscal retear. [ABSTRACT FROM AUTHOR]

Growth and maturation occur in a predictable pattern throughout the body and within each individual bone. In the appendicular skeleton, endochondral ossification predominates in long bones and growth plates. The ends of these long bones are sites of relative weakness in the immature skeleton and prone to injury from acute insult and overuse. We present the normal histoanatomy and physiology of the growth plate complex, highlighting the unique contribution of each component and shared similarities between primary and secondary complexes. Components of the growth plate complex include the physis proper, subjacent vascularity within the growth cartilage, and the ossification front. The second section describes imaging considerations and features of normal and abnormal growth. Finally, we review the Salter-Harris classification for acute fractures and offer examples of characteristic overuse injury patterns involving the epiphyseal (proximal humerus and distal radius), apophyseal (medial epicondyle and tibial tubercle), and secondary growth plate complexes (medial femoral condyle and capitellar osteochondritis dissecans). This article provides a foundation and basic framework to better understand and anticipate potential complications and growth disturbances and to ensure optimal follow-up and early intervention when treatment can be less invasive. [ABSTRACT FROM AUTHOR]

The pediatric elbow is a complex joint that undergoes rapid growth and development. The normal anatomy of the elbow varies depending on the age of the patient, which can be challenging for imaging interpretation. This article reviews developmental variants and common pathologies of the pediatric elbow, with a focus on their radiologic features. Normal anatomy and development of the pediatric elbow are discussed, including the six ossification centers and elbow alignment. Congenital anomalies such as longitudinal deficiencies of the upper extremity are reviewed. Some common injuries that affect the elbow, such as supracondylar fracture, lateral condyle fracture, medial epicondyle avulsion, and radial head dislocation are also described. [ABSTRACT FROM AUTHOR]

During normal development, imaging findings in the immature knee joint may mimic pathology or indicate transient sites of weakness, prone to injury. This article reviews the development of the knee joint, age- and maturation-dependent imaging considerations, and various developmental variants that can be encountered, subdivided into those that involve the tibiofemoral and patellofemoral compartments, soft tissues, and osseous components. The tibiofemoral compartment section reviews the focal periphyseal edema zone (FOPE), ossification variants of the femoral condyles, distal femoral metaphyseal cortical irregularity from periosteal traction, and the metaphyseal subperiosteal stripe, which should be distinguished from pathologic mimickers such as endochondral ossification dysfunction, osteochondritis dissecans (OCD), fibroosseous lesion, periosteal and subcortical pathologies. The patellofemoral compartment section includes a review of partite patella, dorsolateral defect, variant trochlear morphology, and maturation-dependent sites of transient weakness that are prone to injury from repetitive overuse (Sinding-Larsen-Johansson syndrome and Osgood-Schlatter disease) and avulsion fractures (patellar sleeve and tibial tubercle avulsions). Finally, soft tissue (discoid lateral meniscus, meniscal flounce, anterior cruciate ligament variants) and osseous components (meniscal ossicle, fabella, and cyamella) are reviewed. [ABSTRACT FROM AUTHOR]

Year-round participation in youth sport that involves high levels of repetitive movement fosters an environment in which overuse injuries are likely to occur. Epiphyseal primary physeal stress injuries (PSIs), unique to skeletally immature athletes, are a particular concern, given their potential for growth disturbance. Initially observed in Little League baseball players, these injuries are now known to affect the long bones around the shoulder, elbow, wrist, hand, knee, ankle, and foot of skeletally immature athletes involved in a variety of sport activities. This article offers an epidemiological and radiologic perspective on the extent and distribution of epiphyseal PSIs in youth sport. We also review a novel framework for understanding the pathophysiologic mechanisms causing these injuries. This information is essential for the early identification of epiphyseal PSIs and devising preventive measures that can reduce a delayed diagnosis and long-term morbidity. Preventing and reducing injury to the epiphyseal growth plates is essential because impairment and dysfunction can result in lifelong morbidity and a risk of premature osteoarthritis. [ABSTRACT FROM AUTHOR]

Increase in youth sports participation, longer duration of play, and earlier starting points have increased the prevalence of acute and repetitive overuse musculoskeletal injuries. This rise in injury rates has led to increased efforts to better understand the susceptible sites of injury that are unique to the growing immature skeleton. Upper extremity injuries are currently the best studied, particularly those that occur among pediatric baseball players and gymnasts. The weak link in skeletally immature athletes is the growth plate complex that includes those injuries located at the epiphyseal and apophyseal primary physes and the peripherally located secondary physes. This article reviews the anatomy and function of these growth plate complexes, followed by a discussion of the pathophysiologic mechanisms, spectrum of imaging findings, and existing evidence-based guidelines for injury prevention and return to play. [ABSTRACT FROM AUTHOR]

Context Almonertinib is primarily metabolized by CYP3A4, so it could interact with a variety of drugs metabolized by CYP3A4, leading to the changes of systemic exposure.Objective For the purpose of this experiment, an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay with accuracy and simplicity was optimized and fully validated for the simultaneous quantitative determination of almonertinib and its metabolite HAS-719, and drug-drug interactions (DDI) between almonertinib and nicardipine in vivo and in vitro was researched.Materials and methods Detection of analytes was achieved by UPLC-MS/MS coupled with multiple reaction monitoring (MRM) in the positive ion mode with ion transitions of m/z 526.01 → 72.04 for almonertinib, m/z 512.18 → 455.08 for HAS-719 and m/z 447.16 → 128.11 for IS, respectively.Results There was favourable linearity in the 0.5–200 ng/mL calibration range for almonertinib and 0.5–100 ng/mL for HAS-719. The lower limit of quantification (LLOQ) for both analytes was 0.5 ng/mL. The precision, accuracy, stability, matrix effect and extraction recovery required for methodological validation were consistent with the requirements of FDA guideline. Then, the UPLC-MS/MS assay was employed successfully on the interactions of almonertinib and nicardipine in vivo and in vitro. The half-maximal inhibitory concentration (IC50) was 1.19 μM in rat liver microsomes (RLM), where nicardipine inhibited the metabolism of almonertinib with a mixed inhibitory mechanism. In pharmacokinetic experiments of rats, it was observed that nicardipine could significantly alter the pharmacokinetic profiles of almonertinib, including AUC(0-∞), AUC(0-t) and Cmax, but had no effect on the metabolism of HAS-719.Conclusion According to the findings, it was indicated that nicardipine could inhibit the metabolism of almonertinib in vitro and in vivo.

Context The global prevalence of type 2 diabetes mellitus (T2DM) has increased significantly in recent decades. Despite numerous studies and systematic reviews, there is a gap in comprehensive and up-to-date evaluations in this rapidly evolving field.Objective This review provides a comprehensive and current overview of the efficacy of Traditional Chinese Medicine (TCM) in treating T2DM.Methods A systematic review was conducted using PubMed, Web of Science, Wanfang Data, CNKI, and Medline databases, with a search timeframe extending up to November 2023. The search strategy involved a combination of subject terms and free words in English, including ‘Diabetes,’ ‘Traditional Chinese Medicine,’ ‘TCM,’ ‘Hypoglycemic Effect,’ ‘Clinical Trial,’ and ‘Randomized Controlled Trial.’ The studies were rigorously screened by two investigators, with a third investigator reviewing and approving the final selection based on inclusion and exclusion criteria.Results A total of 108 relevant papers were systematically reviewed. The findings suggest that TCMs not only demonstrate clinical efficacy comparable to existing Western medications in managing hypoglycemia but also offer fewer adverse effects and a multitarget therapeutic approach. Five main biological mechanisms through which TCM treats diabetes were identified: improving glucose transport and utilization, improving glycogen metabolism, promoting GLP-1 release, protecting pancreatic islets from damage, and improving intestinal flora.Conclusions TCM has demonstrated significant protective effects against diabetes and presents a viable option for the prevention and treatment of T2DM. These findings support the further exploration and integration of TCM into broader diabetes management strategies.

Microscale energetic materials have garnered considerable attention because they can be integrated in microelectromechanical systems for several potential applications. Hexanitrostilbene (HNS) has been widely utilized in ignition and initiation devices owing to its excellent thermal and shock stability and high sensitivity to short pulse shock waves. To meet the energy release requirements of micro-detonation devices, HNS sticks were prepared using direct ink writing and their reaction and flame propagation properties were studied. HNS particles sized 17.5 µm to 5 µm and ∼500 nm was prepared. Then, the viscosity of HNS-based inks prepared via acoustic resonance technology decreased when the particle size decreased or when the HNS content reduced from 97 wt.%, 95 wt.%, and 92 wt.%, to 90 wt.%. Additionally, the HNS-based inks with different binders exhibited different viscosity. The effect of the inner diameter of needle (0.4 mm, 0.6 mm, and 0.9 mm), printing rate (13 mm/s, 15 mm/s, 17 mm/s, 19 mm/s), and pressure (0.05 MPa, 0.1 MPa, 0.15 MPa, 0.2 MPa) on the width of HNS sticks was also elucidated. HNS-based sticks with a diameter of 0.9 mm underwent self-sustaining combustion reactions, and the burning rate increased from 5.1 mm/s to 6.8 mm/s as the particle size decreased from 17.5 µm to 500 nm. Overall, this work provides an effective approach to prepare microscale HNS for integration into micro-energetic devices.

Context Diabetic retinopathy (DR) is one of the leading causes of vision impairment and blindness among diabetic patients globally. Despite advancements in conventional treatments, the quest for more holistic approaches and fewer side effects persists. Traditional Chinese medicine (TCM) has been used for centuries in managing various diseases, including diabetes and its complications.Objective This review evaluated the efficacy and underlying mechanisms of TCM in the management of DR, providing information on its potential integration with conventional treatment methods.Methods A comprehensive literature review was conducted using PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) with the search terms ‘traditional Chinese medicine’, ‘diabetic retinopathy’, ‘clinical efficacies’ and their combinations. Studies published before 2023 without language restriction were included, focusing on clinical trials and observational studies that assessed the effectiveness of TCM in DR treatment.Results The review synthesized evidence of empirical traditional Chinese formulas, traditional Chinese patent medicines, and isolated phytochemicals on DR treatment. The key mechanisms identified included the reduction of oxidative stress, inflammation, and neovascularization, as well as the improvement in neurovascular functionality and integrity of the retinal blood barrier.Conclusions TCM shows promising potential to manage DR. More large-scale, randomized controlled trials are recommended to validate these findings and facilitate the integration of TCM into mainstream DR treatment protocols.

Abstract Distal cholangiocarcinoma is a rare and highly aggressive malignant tumor. The inherent tumor characteristics and growth pattern of cancer cells pose a challenge for diagnosis and treatment. Chemotherapy resistance leads to limited treatment options for patients with advanced cholangiocarcinoma. However, drug resistance studies in cholangiocarcinoma are often limited by the use of preclinical models that do not accurately replicate the essential features of the disease. In this study, we established and characterized a primary multidrug-resistant distal cholangiocarcinoma cell line, CBC3T-6. STR profiling indicated no evidence of cross-contamination. This cell line remains stable during long-term in vitro culture and is characterized by short doubling times and rapid subcutaneous tumor formation in mice. In addition, among the first-line anticancer drugs for cholangiocarcinoma, CBC3T-6 cells showed varying degrees of resistance to gemcitabine, oxaliplatin, cisplatin, and 5-FU. Whole exome sequencing analysis revealed that CBC3T-6 cells contained a variety of potentially pathogenic somatic cell mutations, such as TP53 and KRAS mutations. ABCB1 mutation as a possible therapeutic target for multidrug resistance. In conclusion, CBC3T-6 cells can be used as a useful tool to study the mechanism of cholangiocarcinoma and develop new therapeutic strategies for multidrug resistance.

Abstract Background Acute compartment syndrome is a rare but serious complication following gynecological surgery in the lithotomy position, potentially resulting in permanent neuromuscular dysfunction or limb loss, making early recognition and prompt management essential. Case presentation A 41-year-old woman underwent a laparoscopic myomectomy for uterine fibroids, during which she was positioned in the high lithotomy and head-down position for 118 min. Six hours post-surgery, she experienced spasmodic pain and swelling in both lower extremities. Thirteen hours after surgery, her symptoms worsened, leading to the diagnosis of acute compartment syndrome in both legs. An emergency bilateral fasciotomy was performed, and the patient fully recovered within two months without any neuromuscular dysfunction. Conclusions ACS should be an important differential diagnosis for lower extremity pain after gynecologic surgery, especially with prolonged lithotomy positioning. Gynecologists should be vigilant for ACS signs and symptoms to prevent delayed diagnosis.

Abstract The damnification of mitochondrion is often considered to be an important culprit of inflammatory bowel disease (IBD), however, there are fewer reports of mechanisms of mitochondria-mediated IBD treatment. Therefore, we first proposed to reboot mitochondrial energy metabolism to treat IBD by capturing the double-sided factor of ROS and creatine (Cr)-assisted energy adjustment. Herein, an oral Cr-modified selenium-based hyaluronic acid (HA) nanogel (HASe-Cr nanogel) was fabricated for treatment of IBD, through ROS elimination and energy metabolism upgradation. More concretely, due to IBD lesion-specific positive charge and the high expression of CD44, HASe-Cr nanogel exhibited dual targeted inflammatory bio-functions, and ROS-driven degradation properties in high-yield ROS levels in inflammation areas. As expected, multifunctional HASe-Cr nanogel could effectively ameliorate IBD-related symptoms, such as mitochondrial biological function restoration, inhibition of M1-like macrophage polarization, gut mucosal reconstruction, microbial ecological repair, etc., thus excellently treating IBD. Overall, the proposed strategy underlined that the great potentiality of HASe-Cr nanogel by restarting mitochondrial metabolic energy in colitis lesions, providing new a pavement of mitochondrion-mediated colitis treatment in clinical applications.

Abstract Background We conducted a study on radiation exposure in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) treated with [177Lu]Lu-DOTA-TATE in China for the first time, aiming to provide guidance and reference for radiation protection in this regard. A total of 30 GEP-NENs patients who received [177Lu]Lu-DOTA-TATE therapy were recruited in the study. We measured the external dose rate (EDR) values of each patient during the injection and 0–6 h post-administration period, as well as the radiation dose (RD) values to healthcare nurses and the surrounding environment. We performed a double exponential curve fitting and estimated the RD to the public from patients discharged at different times after [177Lu]Lu-DOTA-TATE therapy. Results Among the 30 patients, 27 patients completed 4 cycles of [177Lu]Lu-DOTA-TATE treatments, the estimated RD to the public indicated that for adult family members, children above 10 years old, children aged 3–10 and coworkers of the patients, patients could begin daily contact at least 24 h, 48 h, 144 h and 192 h after injection to ensure that the total RD values after four treatments not exceed the limit. During the hospitalization of patients receiving [177Lu]Lu-DOTA-TATE, the cumulative dose received by the administering nurses and to the ward environment were both well below the national RD limits. Conclusions This study conducted a fitting analysis of the decay pattern of EDR values in GEP-NENs patients undergoing [177Lu]Lu-DOTA-TATE therapy, in order to establish guidelines for patient discharge timing and provide recommendations for radiation protection for the general public after patient discharge. Trial registration A Study Comparing Treatment With Lutetium[177Lu] Oxodotreotide Injection to Octreotide LAR in Patients With GEP-NETs, NCT05459844. https://clinicaltrials.gov/study/NCT05459844?cond=NCT05459844&rank=1 . Registered 5 July 2022.

Abstract Background The COVID-19 pandemic has had a profound impact on global mental health, particularly affecting vulnerable groups such as pregnant women. Post-traumatic stress disorder (PTSD) in this population may potentially hinder infant physical development, underscoring the necessity for specific interventions. This study seeks to explore the prevalence of PTSD among pregnant women during the pandemic and its implications for infant physical development, thereby providing evidence to mitigate the adverse effects of the pandemic on maternal and child health. Methods A prospective cohort study was carried out involving 450 pregnant women from December 2022 to February 2023. Data included demographic details, PTSD evaluation using the PTSD Checklist-Civilian version (PCL-C) scale, coping mechanisms, and infant growth indicators at three months postpartum. Statistical methods included descriptive statistics, univariate analysis, and multivariate analysis of covariance (ANCOVA) to control for confounding factors. Results The study enrolled a total of 450 pregnant women. Following exclusions and follow-up attrition, 422 pregnant women were analyzed. There were 72 pregnant women with PTSD and 350 without PTSD. There was no statistically significant difference in birth weight between the two groups of participants. Three months after birth, infants of PTSD-positive mothers exhibited significantly lower weight percentiles at three months (P

Abstract Background Psychological capital can effectively alleviate job burnout and improve career autonomy and job satisfaction. However, there is a lack of research on the mediating role of psychological capital between job burnout and preseneeism in Chinese anesthesia nurses. Aims The mediating role of psychological capital between job burnout and presenteeism based on constructing structural equation models in anesthesia nurses. Methods This study was a cross-sectional study design. From June to July 2024, convenience sampling was used to conduct a questionnaire survey of 568 anesthesia registered nurses in different levels of hospitals in Sichuan Province. The self-designed general information questionnaire, Chinese version of Stanford Invisible Absence Scale (SPS-6), Psychological Capital Scale-Chinese Revised (PCQ) and Maslach Burnout Inventory-General Survey (MBI) were used to investigate the status through the form of questionnaire star. Pearson correlation analysis was used to explore the interaction among psychological capital, job burnout and presenteeism. AMOS 26.0 software was used to further verify the mediating effect of psychological capital between job burnout and preseneeism, and to construct the corresponding path relationship model. Results The scores of psychological capital, job burnout and preseneeism were 93.31 ± 14.33, 56.35 ± 17.67 and 18.96 ± 4.97, respectively. Job burnout of anesthesia nurses was significantly negatively correlated with psychological capital (r=-0.558, P

Abstract Background Evidence has accumulated to demonstrate that intestinal microbiome can inhibit viral infection. However, our knowledge of the signaling pathways and identity of specific commensal microbes that mediate the antiviral response is limited. Zebrafish have emerged as a powerful animal model for study of vertebrate-microbiota interactions. Here, a rhabdoviral infection model in zebrafish allows us to investigate the modes of action of microbiome-mediated antiviral effect. Results We observed that oral antibiotics-treated and germ-free zebrafish exhibited greater spring viremia of carp virus (SVCV) infection. Mechanistically, depletion of the intestinal microbiome alters TLR2-Myd88 signaling and blunts neutrophil response and type I interferon (IFN) antiviral innate immunity. Through 16S rRNA sequencing of the intestinal contents from control and antibiotic(s)-treated fish, we identified a single commensal bacterial species, Cetobacterium somerae, that can restore the TLR2- and neutrophil-dependent type I IFN response to restrict SVCV infection in gnotobiotic zebrafish. Furthermore, we found that C. somerae exopolysaccharides (CsEPS) was the effector molecule that engaged TLR2 to mediate the type I IFN-dependent antiviral function. Conclusions Together, our results suggest a conserved role of intestinal microbiome in regulating type I IFN antiviral response among vertebrates and reveal that the intestinal microbiome inhibits viral infection through a CsEPS-TLR2-type I IFN signaling axis in zebrafish. Video Abstract

Abstract Lipid metabolism reprogramming has emerged as a hallmark of malignant tumors. Lipids represent a complex group of biomolecules that not only compose the essential components of biological membranes and act as an energy source, but also function as messengers to integrate various signaling pathways. In tumor cells, de novo lipogenesis plays a crucial role in acquiring lipids to meet the demands of rapid growth. Increasing evidence has suggested that dysregulated lipid metabolism serves as a driver of cancer progression. Posttranslational modifications (PTMs), which occurs in most eukaryotic proteins throughout their lifetimes, affect the activity, abundance, function, localization, and interactions of target proteins. PTMs of crucial molecules are potential intervention sites and are emerging as promising strategies for the cancer treatment. However, there is limited information available regarding the PTMs that occur in cancer lipid metabolism and the potential treatment strategies associated with these PTMs. Herein, we summarize current knowledge of the roles and regulatory mechanisms of PTMs in lipid metabolism. Understanding the roles of PTMs in lipid metabolism in cancer could provide valuable insights into tumorigenesis and progression. Moreover, targeting PTMs in cancer lipid metabolism might represent a promising novel therapeutic strategy.

Abstract This study profiled global single cell-spatial-bulk transcriptome landscapes of hepatocellular carcinoma (HCC) ecosystem from six HCC cases and a non-carcinoma liver control donor. We discovered that intratumoral heterogeneity mainly derived from HCC cells diversity and pervaded the genome-transcriptome-proteome-metabolome network. HCC cells are the core driving force of taming tumor-associated macrophages (TAMs) with pro-tumorigenic phenotypes for favor its dominant growth. Remarkably, M1-types TAMs had been characterized by disturbance of metabolism, poor antigen-presentation and immune-killing abilities. Besides, we found simultaneous cirrhotic and HCC lesions in an individual patient shared common origin and displayed parallel clone evolution via driving disparate immune reprograms for better environmental adaptation. Moreover, endothelial cells exhibited phenotypically conserved but executed differential functions in a space-dependent manner. Further, the spatiotemporal traits of rapid recurrence niche genes were identified and validated by immunohistochemistry. Our data unravels the great significance of HCC cells in shaping vibrant tumor ecosystems corresponding to clinical scenarios.

Abstract Background This systematic review and meta-analysis aimed to evaluate the impact of perioperative immunonutrition on postoperative outcomes in patients undergoing pancreaticoduodenectomy (PD). Methods Conducted a comprehensive search in PubMed, Embase, Cochrane Library, Medline, and Web of Science databases to identify all randomized controlled trials (RCTs) on the topic of immunonutrition and PD. Subsequently screened literature, extracted data, and assessed the risk of bias in the included studies, and finally conducted a meta-analysis using RevMan 5.3 software. Results The analysis included a total of 10 RCTs with 574 patients, among whom 288 were in the immunonutrition group and 283 in the control group. The meta-analysis revealed a significantly lower incidence of postoperative infection-related complications (OR = 0.45; 95% CI: 0.27–0.74; P = 0.002) and severe postoperative complications (OR = 0.61; 95% CI: 0.38–0.98; P = 0.04) in the immunonutrition group compared to the control group. Additionally, patients in the immunonutrition group had a significantly shorter length of hospital stay (MD= -1.87; 95%CI -3.29 - -0.44; P = 0.01). However, the analysis revealed no statistically significant difference in the overall complication rate between the two groups (P = 0.67). Furthermore, the incidence of specific complications and perioperative mortality rates also did not demonstrate any statistically significant differences (all P > 0.05). Conclusions Perioperative immunonutrition in PD patients can reduce postoperative infection-related complications, but more high-quality RCTs are needed for further validation.

Abstract Background Diabetic retinopathy (DR), a prevalent complication in patients with type 2 diabetes, has attracted increasing attention. Recent studies have explored a plausible association between retinopathy and significant liver fibrosis. The aim of this investigation was to develop a sophisticated machine learning (ML) model, leveraging comprehensive clinical datasets, to forecast the likelihood of significant liver fibrosis in patients with retinopathy and to interpret the ML model by applying the SHapley Additive exPlanations (SHAP) method. Methods This inquiry was based on data from the National Health and Nutrition Examination Survey 2005–2008 cohort. Utilizing the Fibrosis-4 index (FIB-4), liver fibrosis was stratified across a spectrum of grades (F0-F4). The severity of retinopathy was determined using retinal imaging and segmented into four discrete gradations. A ten-fold cross-validation approach was used to gauge the propensity towards liver fibrosis. Eight ML methodologies were used: Extreme Gradient Boosting, Random Forest, multilayer perceptron, Support Vector Machines, Logistic Regression (LR), Plain Bayes, Decision Tree, and k-nearest neighbors. The efficacy of these models was gauged using metrics, such as the area under the curve (AUC). The SHAP method was deployed to unravel the intricacies of feature importance and explicate the inner workings of the ML model. Results The analysis included 5,364 participants, of whom 2,116 (39.45%) exhibited notable liver fibrosis. Following random allocation, 3,754 individuals were assigned to the training set and 1,610 were allocated to the validation cohort. Nine variables were curated for integration into the ML model. Among the eight ML models scrutinized, the LR model attained zenith in both AUC (0.867, 95% CI: 0.855–0.878) and F1 score (0.749, 95% CI: 0.732–0.767). In internal validation, this model sustained its superiority, with an AUC of 0.850 and an F1 score of 0.736, surpassing all other ML models. The SHAP methodology unveils the foremost factors through importance ranking. Conclusion Sophisticated ML models were crafted using clinical data to discern the propensity for significant liver fibrosis in patients with retinopathy and to intervene early. Practice implications Improved early detection of liver fibrosis risk in retinopathy patients enhances clinical intervention outcomes.

Abstract Background The aim of this study was to assess the prognostic significance of serum direct bilirubin (DBIL) for patients newly diagnosed with myelodysplastic syndromes (MDS). Methods The clinical, laboratory, and follow-up data of MDS patients were collected, and the associations of DBIL levels with overall survival (OS) and leukemia-free survival (LFS) were analyzed. Result In total, 262 MDS patients were assigned to the high DBIL level group or the normal DBIL level group in the retrospective study. High DBIL was associated with older age, reduced hemoglobin, higher levels of β2-microglobin, lactate dehydrogenase, and serum ferritin, along with the number of co-mutations (> 1) and a higher frequency of ASXL1, KIT, and KRAS mutations. Multivariate analyses found that high DBIL level was an independent adverse predictor for OS (p = 0.002, hazard ratio = 2.723, 95%CI = 1.442–5.143) but not for LFS (p = 0.057, hazard ratio = 1.678, 95%CI = 0.986–2.857). A novel nomogram based on DBIL, sex, age, β2-microglobulin, lactate dehydrogenase, the Revised International Prognostic Scoring System (IPSS-R) was constructed, which demonstrated superior accuracy compared with the IPSS-R (C-index, 0.790 vs. 0.731, respectively). Conclusion An elevated DBIL level was identified as an independent adverse prognostic factor for MDS patients. An individualized prediction model was established and validated to improve prediction of OS and LFS.

Abstract Background Recurrent gliomas rapidly progress and have high mortality and poor prognosis in the central nervous system. Therefore, further investigation of prognostic and therapeutic markers is needed. Methods The mRNA expression, clinical data, and coagulation-related genes (CRGs) associated with recurrent glioma were obtained and calculated from the Chinese Glioma Genome Atlas and Kyoto Encyclopedia of Genes and Genomes databases. The significant CRGs were calculated by Weighted gene co-expression network analysis and PPI network. A prediction model was constructed using the least absolute shrinkage and selection operator regression analysis. Recurrent gliomas were stratified into high and low-risk groups based on the median risk score (RS). The Kaplan–Meier curve was used to analyze the difference in overall survival (OS) between these groups, while the receiver operating characteristic (ROC) curve was used to evaluate the accuracy of the gene model at 1-, 3-, and 5-years. Clinical factors, including age, gender, MGMT methylation status, radiotherapy, chemotherapy, and RS, were included in the univariate and multivariate regression analysis. A prognostic nomogram and calibration curve were established based on these factors. Results Overall, seven CRGs associated with the prognosis were identified, including BTK, ITGB1, GNAI3, CFH, LYN, CFI, and F3. OS and survival rates were lower in the high-risk group compared with the low-risk group. The ROC curve demonstrated the area under the curve values >0.65 at 1-, 3-, and 5-years, confirming the reliability of the prognostic model. The univariate regression analysis indicated that tumor grade (grades 2, 3, and 4), histopathology (GBM or not), chemotherapy, IDH mutation, and 1p19q co-deletion status were independent prognostic indicators. Univariate and multivariate regression analyses indicated that RS was an independent prognostic factor for patients with recurrent glioma. Immune analysis revealed low infiltration of resting dendritic cells and high expression of programmed death receptor 1 in the high-risk group. Conclusion This study comprehensively investigated the correlation between CRGs and recurrent glioma prognosis, offering crucial insights for further research into glioma recurrence mechanisms and treatment strategies.

Abstract Hepatocellular carcinoma (HCC) remains one of the most prevalent malignant tumors globally, characterized by high incidence and mortality rates. Despite ongoing research, the underlying molecular mechanisms of HCC development are not yet fully understood. Utilizing bioinformatic analysis, real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blot assays, we identified that the expression of specificity protein 1 (Sp1) was significantly elevated in HCC cells compared to normal cells. Knockdown of the Sp1 gene led to a marked reduction in the viability and clonogenic potential of HCC cells. Further investigation revealed that the succinylation level of Sp1 was also increased in HCC cells. The upregulation of Sp1 expression was attributed to its succinylation, mediated by KAT2A, with lysine (K)562 identified as the succinylation site. Additionally, KAT2A and Sp1 were found to influence the upregulation of mTOR phosphorylation. Collectively, these findings suggest that KAT2A-promoted succinylation of Sp1 enhances the proliferative capacity of HCC cells by activating the mTOR pathway, providing a theoretical foundation for potential therapeutic strategies against HCC.

Abstract The complexities encountered in microbial metabolic engineering continue to elude prediction and design. Unravelling these complexities requires strategies that go beyond conventional genetics. Using multiplex mutagenesis with double stranded (ds) DNA, we extend the multiplex repertoire previously pioneered using single strand (ss) oligonucleotides. We present ReaL-MGE (Recombineering and Linear CRISPR/Cas9 assisted Multiplex Genome Engineering). ReaL-MGE enables precise manipulation of numerous large DNA sequences as demonstrated by the simultaneous insertion of multiple kilobase-scale sequences into E. coli, Schlegelella brevitalea and Pseudomonas putida genomes without any off-target errors. ReaL-MGE applications to enhance intracellular malonyl-CoA levels in these three genomes achieved 26-, 20-, and 13.5-fold elevations respectively, thereby promoting target polyketide yields by more than an order of magnitude. In a further round of ReaL-MGE, we adapt S. brevitalea to malonyl-CoA elevation utilizing a restricted carbon source (lignocellulose from straw) to realize production of the anti-cancer secondary metabolite, epothilone from lignocellulose. Multiplex mutagenesis with dsDNA enables the incorporation of lengthy segments that can fully encode additional functions. Additionally, the utilization of PCR to generate the dsDNAs brings flexible design advantages. ReaL-MGE presents strategic options in microbial metabolic engineering.

Abstract Crystalline silica (CS) particle exposure leads to silicosis which is characterized as progressive fibrosis. Fibroblasts are vital effector cells in fibrogenesis. Emerging studies have identified immune sentinel roles for fibroblasts in chronic disease, while their immune-modulatory roles in silicosis remain unclear. Herein, we show that group 2 innate lymphoid cell (ILC2) conversion to ILC1s is closely involved in silicosis progression, which is mediated by activated fibroblasts via interleukin (IL)−18. Mechanistically, Notch3 signaling in mechanics-activated fibroblasts modulates IL-18 production via caspase 1 activity. The mouse-specific Notch3 knockout in fibroblasts retards pulmonary fibrosis progression that is linked to attenuated ILC conversion. Our results indicate that activated fibroblasts in silicotic lungs are regulators of ILC2–ILC1 conversion, associated with silicosis progression via the Notch3–IL-18 signaling axis. This finding broadens our understanding of immune-modulatory mechanisms in silicosis, and indicates potential therapeutic targets for lung fibrotic diseases.

Abstract Background This study investigated the factors influencing the prognosis of children with steroid-resistant nephrotic syndrome (SRNS) in patients from the Guangxi region. Methods We retrospectively analyzed clinical and pathological data of 279 patients with SRNS from six tertiary hospitals in Guangxi. Clinical data were compared between initial (I-SRNS) and secondary (S-SRNS) steroid resistance subgroups and Cox regression analysis was used to determine risk factors for chronic kidney disease (CKD) and CKD stage 5 (CKD5) in patients with SRNS. Results The median age of onset was 54 months. Thirty-three patients had extra-kidney manifestations. Fifty-two, 24, 57, 33, and 41 patients had hypertension, acute kidney injury, vitamin D deficiency, high intraocular pressure, and dwarfism, respectively. One hundred eighty-two and 92 patients had I-SRNS and S-SRNS, respectively. There were significant differences in sex, ethnicity, family history, incidence of hematuria, clinical classification, efficacy of immune agents, and prognosis between groups (P

Abstract In a retrospective analysis of clinical data from 587 DLBCL (diffuse large B-cell lymphoma) patients in China, 13.8% of cases were associated with HBV (hepatitis B virus) infection, leading to distinct clinical features and poorer prognosis. Moreover, HBV infection has a more pronounced impact on the survival of the GCB (germinal center B-cell-like) type DLBCL patients compared to the ABC (activated B-cell-like) type. In this study, we found that the expression of LncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was downregulated in the HBV-infected GCB-type DLBCL patients, and the HBV core protein (HBX) directly inhibited the MALAT1 expression in DLBCL cells. Notably, the overexpression of HBX could attenuate the Erastin-induced ferroptosis in the GCB-type DLBCLs, while MALAT1 re-expression restored sensitivity in the HBX-overexpressing DLBCLs in vitro and in vivo. Mechanistically, MALAT1 competitively hindered SFPQ (splicing factor proline and glutamine-rich) from effectively splicing the pre-mRNA of SLC7A11 (solute carrier family 7 member 11), due to a shared TTGGTCT motif, which impeded the SLC7A11 pre-mRNA maturation and hence diminished its negative regulation on ferroptosis. Together, our study identified HBX’s role in inhibiting MALAT1 expression, promoting SFPQ-mediated splicing of SLC7A11 pre-mRNA, and reducing the GCB-type DLBCL sensitivity to Erastin-induced ferroptosis. Combined with the recent studies that ferroptosis may be involved in the occurrence and development of DLBCL, these findings explain our clinical data analysis that DLBCL patients with low expression of MALAT1 have poorer prognosis and shorter overall survival, and provide a valuable therapeutic target for the HBV-infected GCB-type DLBCL patients.

Abstract Background Ki67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem). Method Retrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence. Results In control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p

Abstract. Background:. Uterine fibroids (UFs), the most common tumors in women worldwide, may reduce quality of life and daily activities and even lead to adverse fertility and general health events in patients, causing significant societal health and financial burdens. The objective of this study was to evaluate the global burden through epidemiological trends and examine the potential risk factors for UFs at the national level. Methods:. Data on the incidence, prevalence, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized prevalence rates (ASPRs), and age-standardized DALY rates for UFs were collected, and the associations with the Human Development Index (HDI) and fertility were evaluated. The age trends in the average annual percent change (AAPC) of the incidence and prevalence rates of UFs were evaluated by joinpoint regression analysis. The associations between lifestyle, metabolic, and socioeconomic factors and the ASIRs of UFs were examined using multivariable linear regression analysis. Results:. The worldwide incidence and prevalence of UFs have been increasing in the past decade, with AAPCs of 0.27% in the incidence rate and 0.078% in the prevalence rate. During 2010–2019, significant increasing trends in UF ASIR were observed in 52 of 88 countries. The age-specific incidence and prevalence of UFs in most age groups showed increasing trends except for 45–54-year-old women which showed no significant trend. Ecological analysis demonstrated no relationship between the incidence of UFs and the HDI but an inverse association with fertility. The incidence of UFs was positively correlated with alcohol intake, hypertension, overweight, and obesity and negatively correlated with smoking. Conclusion:. With the increasing incidence and prevalence worldwide, effective targeted prevention and control of relevant risk factors at the national level should be encouraged to reduce the disease burden of UFs.

The effects of covering technology and the combined membrane covering with biochar on nutritional elements content during the aerobic composting process of agricultural waste were studied. The results showed that the concentration effect of organic matter degradation during composting increased the nitrogen, phosphorus, and potassium contents in all treatment groups. The proportion of available phosphorus and available potassium also increased to varying degrees. Compared with composting without an expanded poly(tetrafluoroethylene) (PTFE) covering with 0.2 to 0.4 µm pores, the covered composting increased the total nitrogen, total phosphorus, total potassium, available phosphorus, and available potassium contents by 13.1%, 12.6%, 7.4%, 21.5%, and 16.6%, respectively, while the addition of biochar to polymer membrane-covered composting increased the total nitrogen, total phosphorus, total potassium, available phosphorus, and available potassium contents by 19.7%, 13.7%, 8.3%, 18.0%, and 20.2%, respectively. This study indicated that membrane covering technology can effectively increase the nutrient element contents in compost products and the availability of phosphorus and potassium and that the addition of biochar enhances these effects.

Abstract Background Gliomas are the most common malignant brain tumors characterized by angiogenesis and invasive growth. A detailed understanding of its molecular characteristics could provide potential therapeutic targets. In the present study, we sought to explore the key gene CXCL8 in methionine metabolism in gliomas and its potential role in angiogenesis. Methods U251 glioma cells were divided into control and methionine-restriction tolerant (constructed with 1/4 of the standard level of methionine in the culture medium) groups for transcriptome and metabolome analysis. To confirm the functions and mechanism of CXCL8 in glioma, heat map, volcano map, Go enrichment, gene set enrichment analysis (GSEA), protein–protein interaction network analysis, RT-PCR, western blotting assays, chicken embryo chorioallantoic membrane (CAM) test, chicken embryo yolk sac membrane (YSM) test and transplantation tumor nude mice model were performed. The TCGA database, CGGA database and clinical tissue samples were used to analyze CXCL8’s significance on prognosis for patients with glioma. Results CXCL8 expression was significantly up-regulated in methionine-restricted tolerance cells, it also activated vascular system development and triggered angiogenesis. CXCL8 expression is negatively correlated with survival prognosis in gliomas. Conclusions Glioma cells promote angiogenesis in methionine-restricted environments through the activation of CXCL8, compensating for nutrient deprivation, and possibly contributing to the failure of antiangiogenic therapy.

Abstract Objective This study aims to evaluate the efficacy and safety of 3D printing technology in brachytherapy for cervical cancer, comparing its outcomes with conventional free hand implantation brachytherapy. Methods A total of 50 cervical cancer patients treated at the First Affiliated Hospital of Gannan Medical College from January 2019 to July 2023 were included in this study. Patients were divided into two groups: 25 patients received intensity-modulated radiotherapy (IMRT) combined with 3D-printed brachytherapy, and 25 patients underwent IMRT combined with free hand brachytherapy implantation. Key indicators analyzed included short-term therapeutic effects, survival outcomes, operation times, the number of CT scans, the number of needles inserted, dosimetric parameters, and complications. Results The use of 3D-printed brachytherapy significantly improved the safety of radiation therapy operations, especially for large tumors (≥ 30 mm), by providing more precise dose distribution and reducing the radiation doses received by critical organs such as the bladder and rectum. Compared to the artificial implant group (88% prevalence), the 3D-printed brachytherapy group showed a significantly lower incidence of radiation enteritis (29.2% prevalence, p

Biomass, as a renewable energy source, features wide availability, multiple functions, and carbon neutralization. The high-value resource utilization of biomass is conducive to reducing reliance on high-carbon fossil energy, ensuring national energy security, and curbing environmental pollution, aligning with the needs of China's "dual carbon" national strategy. Pyrolysis, as the foundation of biomass thermochemical conversion, is one of the best technologies to achieve a high-value utilization of biomass energy. However, it has some core issues such as low bio-oil yield and poor quality. To overcome these problems, a cryogenic technology was innovatively applied to the field of biomass pyrolysis, and a new biomass oil production method of "cryogenic + fast pyrolysis" was proposed to increase the yield and quality of pyrolytic bio-oil. Taking two types of crop straw as experimental research objects, the rapid freezing pretreatment method with liquid nitrogen was adopted to study the evolution mechanism of the product distribution and composition of biomass pyrolysis under cryogenic pretreatment. The experiments show that compared with conventional pyrolysis, the increase in the bio-oil yield after cryogenic pretreatment of biomass pyrolysis can reach 14.16% to 23.73%, and the cryogenic pretreatment temperature has a positive correlation with the bio-oil yield, and the maximum bio-oil yield (22.3% to 26.3%) is reached at −90 ℃, exceeding the bio-oil yield of the aluminum method by 8.50% to 22.71%. The cryogenic pretreatment has a significant transformation effect on the composition of the bio-oil, and the content of benzene series (BTEX) and phenolic substances in the bio-oil composition increases significantly, with the maximum increase of 43.61% and 12.45%, respectively. The cryogenic pretreatment of liquid nitrogen inhibited the release of CO2 and CO in biomass pyrolysis gas, and the proportion of components decreased by 7.2%−29.7%. In addition, the inhibition of the release of CO2 and CO in the biomass pyrolysis gas and the increase of CH4 and H2 by cryogenic pretreatment increase by 0.2% to 14.7%. Moreover, the increase in C content and the decrease in O content in the solid product under cryogenic pretreatment are conducive to improving the combustibility of biochar and reducing its risk of spontaneous combustion.

Abstract The levels of fasting-state serum bile acids (BAs) in individuals with polycystic ovary syndrome (PCOS) differ from those of control subjects. However, there is a lack of research on the BAs profile in lean women with PCOS and whether these changes are linked to the host metabolism. Therefore, our objective was to investigate the synthesis and metabolism of serum BAs in lean women with PCOS and assess the correlation between BAs and clinical characteristics. This study employed a cross-sectional design of lean women with PCOS (n = 240) in comparison to a control group (n = 80) consisting of healthy lean women. The findings revealed significant increases in the levels of non-12-OH BAs and chenodeoxycholic acid (CDCA)% (both P