Clinical and ultrasound features of 46 children with suppurative osteoarthritis: experience from two centers.

OBJECTIVE: Diagnosing musculoskeletal infections in children is challenging. In recent years, with the advancement of ultrasound technology, high-resolution ultrasound has unique advantages for musculoskeletal children. The aim of this work is to summarize the ultrasonographic and clinical characteristics of children with pyogenic arthritis and osteomyelitis. This study provides a simpler and more effective diagnostic basis for clinical treatment. METHODS: Fifty children with osteomyelitis or arthritis were diagnosed via ultrasound, and the results of the ultrasound diagnosis were compared with those of magnetic resonance imaging and surgery. Clinical and ultrasound characteristics were also analyzed. RESULTS: Out of 50 patients, 46 were confirmed to have suppurative infection by surgical and microbiological examination. Among these 46 patients, 26 were diagnosed with osteomyelitis and 20 had arthritis. The manifestations of osteomyelitis were subperiosteal abscess (15 patients), bone destruction (17 patients), bone marrow abscess (9 patients), and adjacent joint abscess (13 patients). Osteomyelitis mostly affects the long bones of the limbs, femur and humerus (10 and 9 patients, respectively), followed by the ulna, radius, tibia and fibula (one patient each). The manifestations of arthritis were joint pus (20 patients) and joint capsule thickening (20 patients), and hip dislocation (8 patients). All the patients had arthritis involving the hip joint. CONCLUSION: Subperiosteal abscess, bone destruction, and joint abscess with dislocation are ultrasonographic features of pyogenic osteoarthritis. The findings of this work can improve the early diagnosis and differentiation of pyogenic osteoarthritis and provide a reliable basis for treatment.

Brain functional connectivity alterations in patients with anterior cruciate ligament injury.

Recent advancements in neuroimaging have illustrated that anterior cruciate ligament (ACL) injuries could impact the central nervous system (CNS), causing neuroplastic changes in the brain beyond the traditionally understood biomechanical consequences. While most of previous functional magnetic resonance imaging (fMRI) studies have focused on localized cortical activity changes post-injury, emerging research has suggested disruptions in functional connectivity across the brain. However, these prior investigations, albeit pioneering, have been constrained by two limitations: a reliance on small-sample participant cohorts, often limited to two to three patients, potentially limiting the generalizability of findings, and an adherence to region of interest based analysis, which may overlook broader network interactions. To address these limitations, our study employed resting-state fMRI to assess whole-brain functional connectivity in 15 ACL-injured patients, comparing them to matched controls using two distinct network analysis methods. Using Network-Based Statistics, we identified widespread reductions in connectivity that spanned across multiple brain regions. Further modular connectivity analysis showed significant decreases in inter-modular connectivity between the sensorimotor and cerebellar modules, and intra-modular connectivity within the default-mode network in ACL-injured patients. Our results thus highlight a shift from localized disruptions to network-wide dysfunctions, suggesting that ACL injuries induce widespread CNS changes. This enhanced understanding has the potential to stimulate the development of strategies aiming to restore functional connectivity and improve recovery outcomes.

Mesenchymal Stem Cell-Derived Extracellular Vesicles in Bone-Related Diseases: Intercellular Communication Messengers and Therapeutic Engineering Protagonists.

Extracellular vesicles (EVs) can deliver various bioactive molecules among cells, making them promising diagnostic and therapeutic alternatives in diseases. Mesenchymal stem cell-derived EVs (MSC-EVs) have shown therapeutic potential similar to MSCs but with drawbacks such as lower yield, reduced biological activities, off-target effects, and shorter half-lives. Improving strategies utilizing biotechniques to pretreat MSCs and enhance the properties of released EVs, as well as modifying MSC-EVs to enhance targeting abilities and achieve controlled release, shows potential for overcoming application limitations and enhancing therapeutic effects in treating bone-related diseases. This review focuses on recent advances in functionalizing MSC-EVs to treat bone-related diseases. Firstly, we underscore the significance of MSC-EVs in facilitating crosstalk between cells within the skeletal environment. Secondly, we highlight strategies of functional-modified EVs for treating bone-related diseases. We explore the pretreatment of stem cells using various biotechniques to enhance the properties of resulting EVs, as well as diverse approaches to modify MSC-EVs for targeted delivery and controlled release. Finally, we address the challenges and opportunities for further research on MSC-EVs in bone-related diseases.

Nitric oxide mediates red light-induced perylenequinone production in Shiraia mycelium culture.

Perylenequinones (PQs) from bambusicolous Shiraia fungi serve as excellent photosensitizers for photodynamic therapy. However, the lower yield of PQ production in mycelium cultures is an important bottleneck for their clinical application. Light has long been recognized as a pivotal regulatory signal for fungal secondary metabolite biosynthesis. In this study, we explored the role of nitric oxide (NO) in the growth and PQ biosynthesis in mycelium cultures of Shiraia sp. S9 exposed to red light. The continuous irradiation with red light (627 nm, 200 lx) suppressed fungal conidiation, promoted hyphal branching, and elicited a notable increase in PQ accumulation. Red light exposure induced NO generation, peaking to 81.7 µmol/g FW on day 8 of the culture, with the involvement of nitric oxide synthase (NOS)- or nitrate reductase (NR)-dependent pathways. The application of a NO donor sodium nitroprusside (SNP) restored conidiation of Shiraia sp. S9 under red light and stimulated PQ production, which was mitigated upon the introduction of NO scavenger carboxy-PTIO or soluble guanylate cyclase inhibitor NS-2028. These results showed that red light-induced NO, as a signaling molecule, was involved in the regulation of growth and PQ production in Shiraia sp. S9 through the NO-cGMP-PKG signaling pathway. While mycelial H2O2 content exhibited no significant alternations, a transient increase of intracellular Ca2+ and extracellular ATP (eATP) content was detected upon exposure to red light. The generation of NO was found to be interdependent on cytosolic Ca2+ and eATP concentration. These signal molecules cooperated synergistically to enhance membrane permeability and elevate the transcript levels of PQ biosynthetic genes in Shiraia sp. S9. Notably, the combined treatment of red light with 5 µM SNP yielded a synergistic effect, resulting in a substantially higher level of hypocrellin A (HA, 254 mg/L), about 3.0-fold over the dark control. Our findings provide valuable insights into the regulation of NO on fungal secondary metabolite biosynthesis and present a promising strategy involving the combined elicitation with SNP for enhanced production of photoactive PQs and other valuable secondary metabolites in fungi.

The complete chloroplast genome of Lagochilus ilicifolius Bunge ex Bentham, Labiat. Gen. 1834 (Lamiaceae) and its phylogenetic analysis.

Lagochilus ilicifolius Bunge ex Bentham, Labiat. Gen is a perennial herb with much-branched stems native to Nei Mongol, Ningxia, Gansu, N Shaanxi. It can be used clinically as a hemostatic agent. The chloroplast genome length is 151,466 bp. It contained two inverted repeat regions of 25,660 bp each, a large single-copy region of length 82,504 bp, and a small single-copy region of length 17,642 bp. Also, the GC content is 38.6%. There were 133 genes annotated, including 88 known protein-coding genes, 37 tRNAs, and eight rRNAs. The phylogenetic tree was constructed using Bayesian method for plastome data of 29 species. The entire chloroplast genome of L. ilicifolius within the Lamiaceae is the first to reveal genetic taxonomy at the molecular level, and the new phylogenetic tree data can be used for future evolutionary studies.

Preliminary exploration of animal models of congenital choledochal cysts.

BACKGROUND: Various animal models have been used to explore the pathogenesis of choledochal cysts (CCs), but with little convincing results. Current surgical techniques can achieve satisfactory outcomes for treatment of CCs. Consequently, recent studies have focused more on clinical issues rather than basic research. Therefore, we need appropriate animal models to further basic research. AIM: To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs. METHODS: Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group, sham surgical group, or control group. A rat model of CC was established by partial ligation of the bile duct. The reliability of the model was confirmed by measurements of serum biochemical indices, morphology of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues. RESULTS: Dilation classified as mild (diameter, ≥ 1 mm to < 3 mm), moderate (≥ 3 mm to < 10 mm), and severe (≥ 10 mm) was observed in 17, 17, and 2 rats in the surgical group, respectively, while no dilation was observed in the control and sham surgical groups. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery, while direct bilirubin, total bilirubin, and gamma-glutamyltransferase were further increased 14 d after surgery. Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery. The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues. CONCLUSION: The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC, which may contribute to investigating the pathogenesis of CC.

Association between exposure to multiple metals and stress urinary incontinence in women: a mixture approach.

There is limited evidence linking exposure to heavy metals, especially mixed metals, to stress urinary incontinence (SUI). This study aimed to explore the relationship between multiple metals exposure and SUI in women. The data were derived from the National Health and Nutrition Examination Survey (NHANES), 2007-2020. In the study, a total of 13 metals were analyzed in blood and urine. In addition, 5155 adult women were included, of whom 2123 (41.2%) suffered from SUI. The logistic regression model and restricted cubic spline (RCS) were conducted to assess the association of single metal exposure with SUI risk. The Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) were used to estimate the combined effect of multiple metals exposure on SUI. First, we observed that blood Pb, Hg and urinary Pb, Cd were positively related to SUI risk, whereas urinary W was inversely related by multivariate logistic regression (all p-FDR < 0.05). Additionally, a significant non-linear relationship between blood Hg and SUI risk was observed by RCS analysis. In the co-exposure models, WQS model showed that exposure to metal mixtures in blood [OR (95%CI) = 1.18 (1.06, 1.31)] and urine [OR (95%CI) = 1.18 (1.03, 1.34)] was positively associated with SUI risk, which was consistent with the results of BKMR model. A potential interaction was identified between Hg and Cd in urine. Hg and Cd were the main contributors to the combined effects. In summary, our study indicates that exposure to heavy metal mixtures may increase SUI risk in women.

Association of Parity with the Risks of Gestational Diabetes and Macrosomia: A Retrospective Cohort Study in Nanjing, China.

BACKGROUND: After implementing the two-child policy, more Chinese women who had a previous delivery had their second child. Nevertheless, the impacts of parity on Gestational Diabetes (GDM) and macrosomia have not been fully confirmed. Therefore, we aimed to analyse the characteristics of pregnancy by parity and evaluate the association of parity with risks of GDM/macrosomia in a Chinese population. METHODS: A total of 193,410 pregnant women (including 148,293 primiparae and 45,117 multiparae) with complete information were included. Univariate and multivariate logistic regression analyses were used to examine the association between parity and risks of GDM/macrosomia. RESULTS: With the gradual implementation of the two-child policy, the proportion of multiparae increased rapidly and then decreased slightly. Multiparae were more likely to be older and have higher intrapartum BMI, as compared to primiparae (P < 0.001). Univariate regression analyses suggested that parity could increase the risks of GDM and macrosomia; while after adjustment, the association between parity and GDM risk disappeared, and the effects of parity on macrosomia risk and birth weight of babies were also weakened. Further, stratified analysis showed that parity only increased the risk of GDM in women over 30 years, and the effects of parity on macrosomia risk and birth weight were more pronounced among women over 30 years compared to women under 30 years. CONCLUSION: Parity was not associated with GDM risk, but mildly associated with macrosomia risk. Particular attention should be paid to multiparae with advanced age to reduce the risks of GDM and macrosomia.

Elongin B promotes breast cancer progression by ubiquitinating tumor suppressor p14/ARF.

Elongin B (ELOB), a pivotal element in the ELOB/c-Cullin2/5-SOCS-box E3 ubiquitin-protein ligase complex, plays a significant role in catalyzing the ubiquitination and subsequent degradation of a broad spectrum of target proteins. Notably, it is documented to facilitate these processes. However, the regulatory role of ELOB in breast cancer remains ambiguous. In this study, through bio-informatic analysis of The Cancer Genome Atlas and Fudan University Shanghai Cancer Center database, we demonstrated that ELOB was over-expressed in breast cancer tissues and was related to unfavorable prognosis. Additionally, pathway enrichment analysis illustrated that high expression of ELOB was associated with multiple cancer promoting pathways, like cell cycle, DNA replication, proteasome and PI3K - Akt signaling pathway, indicating ELOB as a potential anticancer target. Then, we confirmed that both in vivo and in vitro, the proliferation of breast cancer cells could be significantly suppressed by the down-regulation of ELOB. Mechanically, immunoprecipitation and in vivo ubiquitination assays prompted that, as the core element of Cullin2-RBX1-ELOB E3 ligase (CRL2) complex, ELOB regulated the ubiquitination and the subsequent degradation of oncoprotein p14/ARF. Moreover, the anticancer efficacy of erasing ELOB could be rescued by simultaneous knockdown of p14/ARF. Finally, through analyzing breast cancer tissue microarrays and western blot of patient samples, we demonstrated that the expression of ELOB in tumor tissues was elevated in compared to adjacent normal tissues. In conclusion, ELOB is identified to be a promising innovative target for the drug development of breast cancer by promoting the ubiquitination and degradation of oncoprotein p14/ARF.

Pulmonary scedosporiosis in an intractable immunocompetent host: A case report and literature review.

Pulmonary scedosporiosis is a rare pulmonary infection that often presents with nonspecific symptoms and radiological findings. In this report, we present a case of localized pulmonary scedosporiosis in an immunocompetent patient and analyze a total of 25 immunocompetent patients with pulmonary scedosporiosis. Through this case and the literature, we highlight the importance of considering pulmonary scedosporiosis in patients with nonspecific clinical symptoms and radiological findings resembling aspergilloma. This case and the literature further emphasize the significance of surgical intervention. Regardless of the use of antifungal drugs, surgery should be conducted as soon as possible.

Pitavastatin induces autophagy-dependent ferroptosis in MDA-MB-231 cells via the mevalonate pathway.

Triple-negative breast cancer (TNBC) is more prone to recurrence and metastasis relative to other subtypes of breast cancer, leading to an extremely poor prognosis. The increasing potential chemoresistance of TNBC patients is mainly due to that tumor cells escape from apoptosis. In recent years, statins have demonstrated extensive anti-tumor effects. It is worth noting that statins have more effective anti-tumor effects on TNBC cells and drug-resistant breast cancer cells. Therefore, this study examines the superior cytotoxic effects of statins on TNBC cell lines and further explores their potential therapeutic mechanisms. We detected different cell phenotypes and found that statins significantly reduced the cell viability of TNBC cells. Specifically, pitavastatin showed an obvious induction in cell death, cell cycle arrest and oxidative stress in TNBC MDA-MB-231 cells. The reversal effect of iron chelator desferrioxamine (DFO) on the morphological and molecular biological changes induced by pitavastatin has revealed a new mode of cell death induced by pitavastatin: ferroptosis. This ferroptotic effect was strengthened by the decreased expression of glutathione peroxidase 4 (GPx4) as well as newly discovered ferroptosis suppressor protein 1 (FSP1). The data showed that ferroptotic death of MDA-MB-231 cells is autophagy-dependent and mediated by the mevalonate pathway. Finally, we found that therapeutic oral doses of statins can inhibit the growth of transplanted tumors, which establishes statins as a potential treatment for TNBC patients. In conclusion, we found pitavastatin could induce autophagy-dependent ferroptosis in TNBC cells via the mevalonate pathway which may become a potential adjuvant treatment option for TNBC patients.

Application of hospital-community-home linkage management model in patients with type 2 diabetic nephropathy.

OBJECTIVE: To explore the effect of the hospital-community-home (HCH) linkage management mode in patients with type 2 diabetic nephropathy (DN). METHOD: A total of 80 patients with type 2 DN hospitalised in the Department of Nephrology of our hospital between July 2021 and June 2022 were recruited and subsequently divided into the observation group and the control group using the random number table method, with 40 patients in each group. The control group received routine health education and discharge guidance. The HCH linkage management model was implemented for the observation group based on routine care. The improvements in compliance behaviour, biochemical parameters of renal function, blood glucose level and self-management ability were compared before the intervention and at 3 and 6 months after the intervention. RESULTS: After the intervention, the scores for compliance behaviour of the observation group were better than those of the control group, with a statistically significant difference (P < 0.05). The biochemical indicators of renal function and blood glucose level were significantly lower in the observation group compared with in the control group, with a statistically significant difference (P < 0.05). After the intervention, the observation group showed a great improvement in self-management ability and cognition of the disease, with significant differences (P < 0.05). CONCLUSION: The HCH linkage management mode can improve the compliance behaviour of patients with type 2 DN, effectively improve the renal function and blood sugar level of patients, enhance the self-management ability and cognition of the disease and delay the development of the disease.

Collaborative Enhancement of Consistency and Accuracy in US Diagnosis of Thyroid Nodules Using Large Language Models.

Background Large language models (LLMs) hold substantial promise for medical imaging interpretation. However, there is a lack of studies on their feasibility in handling reasoning questions associated with medical diagnosis. Purpose To investigate the viability of leveraging three publicly available LLMs to enhance consistency and diagnostic accuracy in medical imaging based on standardized reporting, with pathology as the reference standard. Materials and Methods US images of thyroid nodules with pathologic results were retrospectively collected from a tertiary referral hospital between July 2022 and December 2022 and used to evaluate malignancy diagnoses generated by three LLMs-OpenAI's ChatGPT 3.5, ChatGPT 4.0, and Google's Bard. Inter- and intra-LLM agreement of diagnosis were evaluated. Then, diagnostic performance, including accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC), was evaluated and compared for the LLMs and three interactive approaches: human reader combined with LLMs, image-to-text model combined with LLMs, and an end-to-end convolutional neural network model. Results A total of 1161 US images of thyroid nodules (498 benign, 663 malignant) from 725 patients (mean age, 42.2 years ± 14.1 [SD]; 516 women) were evaluated. ChatGPT 4.0 and Bard displayed substantial to almost perfect intra-LLM agreement (κ range, 0.65-0.86 [95% CI: 0.64, 0.86]), while ChatGPT 3.5 showed fair to substantial agreement (κ range, 0.36-0.68 [95% CI: 0.36, 0.68]). ChatGPT 4.0 had an accuracy of 78%-86% (95% CI: 76%, 88%) and sensitivity of 86%-95% (95% CI: 83%, 96%), compared with 74%-86% (95% CI: 71%, 88%) and 74%-91% (95% CI: 71%, 93%), respectively, for Bard. Moreover, with ChatGPT 4.0, the image-to-text-LLM strategy exhibited an AUC (0.83 [95% CI: 0.80, 0.85]) and accuracy (84% [95% CI: 82%, 86%]) comparable to those of the human-LLM interaction strategy with two senior readers and one junior reader and exceeding those of the human-LLM interaction strategy with one junior reader. Conclusion LLMs, particularly integrated with image-to-text approaches, show potential in enhancing diagnostic medical imaging. ChatGPT 4.0 was optimal for consistency and diagnostic accuracy when compared with Bard and ChatGPT 3.5. © RSNA, 2024 Supplemental material is available for this article.

[Distribution Characteristics, Source Analysis and Ecological Risk Assessment of Heavy Metals in the Typical Industry Reclaimed Soil].

To further explore the characteristics of heavy metal pollution and the ecological risk of typical industries in reclaimed soil, based on data from 315 different depth profiles of soil samples collected from 49 plots in Jiading District, Shanghai, the geo-accumulation index and potential ecological risk index were used to evaluate the contents and potential ecological risk of seven heavy metals, namely Cd, Pb, Cu, Zn, Ni, Hg, and As. The APCS-MLR receptor model and PMF positive matrix factorization model were employed to analyze the pollution sources. The results showed that:① except for As, the contents of other heavy metals in the soil of the study area exceeded the Shanghai soil background values to varying degrees. The contents of Cd, Pb, Cu, Zn, Ni, and Hg in the surface soil were 3.54, 2.34, 2.91, 1.20, 3.75, and 4.40 times the background values, respectively. The contents of heavy metals in the soil decreased with the increase in depth, and heavy metals were enriched to a certain extent in the surface soil, indicating that human activities had an impact on the distribution of heavy metals in the soil. ② The APCS-MLR and PMF receptor models identified four main sources of soil heavy metals in the study area. Source 1 (Cu, Zn, and Pb) was a mixture of metal products and automobile manufacturing, source 2 (Ni and Cd) was electroplating enterprises, source 3 (Hg) was mainly from chemical enterprises, and source 4 (As) was natural. The combined use of the two receptor models further improved the accuracy and credibility of source identification. ③ The geo-accumulation index in descending order was Hg(1.54)>Ni(1.32)>Cd(1.21)>Cu(0.96)>Pb(0.64)>Zn(-0.33)>As(-1.02). The potential ecological risk index showed that the comprehensive potential ecological risk index RI value in the study area ranged from 32.50 to 4 910.97, with a mean of 321.40, indicating a strong potential ecological risk. The pollution values of heavy metals Hg, Ni, and Cd in industrial site soil deserve further attention for re-development and utilization purposes.

[Hydrochemical Characteristics and Genesis Mechanism of Groundwater in the Dry Period in the Zhangjiakou Area].

In order to better support the construction of the capital water conservation functional area and ecological environment support area， research on the chemical characteristics of groundwater and its formation mechanism in the dry period in the Zhangjiakou area can provide a great reference for the rational development and utilization of groundwater resources. A total of 41 groups of groundwater samples were collected， and the hydrochemical types， composition characteristics， and control factors of groundwater in the study area were analyzed by using the combined method of descriptive statistical analysis， Piper triplot， correlation analysis， Gibbs plot， and ion ratio. The results showed that the groundwater in the study area was weakly alkaline， with the total hardness and ρ（TDS） ranging from 105.00 mg·L-1 to 1 433.00 mg·L-1 and 137.00 mg·L-1 to 2 286.00 mg·L-1， respectively. The total hardness and TDS mass concentrations of groundwater in the Bashang area were higher than those in the Baxia area. HCO3- and Na+ were the main dominant anions and cations in the groundwater in the study area. The highest overstandard rate of the main components in groundwater was that of total hardness （36.59%）. The overstandard rate and maximum excess multiple of each component in groundwater in the Bashang area were greater than those in the Baxia area. HCO3-Ca·Mg·Na was the main type of groundwater hydrochemistry in the study area， and there was little difference between the Bashang area and the Baxia area. SO42-， Cl-， HCO3-， Na+， and Mg2+ contributed the most to TDS. The chemical characteristics of groundwater were affected by weathering and filtration of rock minerals such as salt rock， albite， and dolomite； cation exchange； and human activities. Evaporative crystallization and atmospheric precipitation contributed to a small part of the main ion source of groundwater in the area. The effect of human activities on groundwater in the Bashang area was greater than that in the Baxia area， and NO3- mainly originated from agricultural activities.

Disorganized adrenocortical zonational structure in COVID-19 patients: Implications of critical illness duration.

Aberrant adrenal function has been frequently reported in COVID-19 patients, but histopathological evidence remains limited. This retrospective autopsy study aims to scrutinize the impact of COVID-19 duration on adrenocortical zonational architecture and peripheral corticosteroid reactivity. The adrenal glands procured from 15 long intensive care unit (ICU)-stay COVID-19 patients, 9 short ICU-stay COVID-19 patients, and 20 matched controls. Subjects who had received glucocorticoid treatment prior to sampling were excluded. Applying hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining, we disclosed that the adrenocortical zonational structure was substantially disorganized in COVID-19 patients, which long ICU-stay patients manifested a higher prevalence of severe disorganization (67%) than short ICU-stay patients (11%; P = 0.0058). The adrenal cortex of COVID-19 patients exhibited a 40% decrease in the zona glomerulosa (ZG) area and a 74% increase in the zona fasciculata (ZF) area (both P < 0.0001) relative to controls. Furthermore, among long ICU-stay COVID-19 patients, the ZG area diminished by 31% (P = 0.0004), and the ZF area expanded by 27% (P = 0.0004) in comparison to short ICU-stay patients. The zona reticularis (ZR) area remained unaltered. Nuclear translocation of corticosteroid receptors in the liver and kidney of long ICU-stay COVID-19 patients was at least 43% lower than in short ICU-stay patients (both P < 0.05). These findings underscore the necessity for clinicians to monitor adrenal function in long-stay COVID-19 patients.

Hand skeletal features of children and adolescents with different growth statuses and periods.

Background: The hand skeletal features of children and adolescents at different growth statuses and development periods, and the correlation between these skeletal features and hand asymmetric force are currently unclear. Thus, this study sought to investigate the hand skeletal features of children and adolescents at different growth statuses and at different periods of development, and the correlation between these skeletal features and asymmetric force in hands. Methods: A retrospective study was performed on subjects aged 4-20 years with good growth status (group A) or short stature (group B). Additional subjects aged 4-20, 21-40, and >40 years were enrolled in groups C, D, and E, respectively. All the subjects underwent left-hand posteroanterior X-ray radiography. Brachymesophalangia-V (BMP-V), conical epiphysis, epiphysis/metaphysis symmetry of the proximal phalanx (ESP), and the angle of the metacarpal-phalangeal axis were analyzed. Results: Of the 654 children and teenagers aged 4-20 years (median: 11 years) enrolled in the study, 432 were allocated to group A, of whom 237 (54.9%) were male and 195 (45.1%) were female, and 222 matched cases were allocated to group B, of whom 112 (50.5%) were male and 110 (49.5%) were female. The first to third ESPs were significantly (P<0.05) greater in group A than in group B, while the first to third angles of the metacarpal-phalangeal axis were significantly (P<0.05) smaller in group A than in group B. The correlation analysis revealed a highly significant (P<0.01) negative correlation between the ESP and angle of the metacarpal-phalangeal axis (r=-0.948, -0.926, -0.940, -0.885, and -0.848, respectively). The incidence of BMP-V was 15.4% in all patients, while that of conical epiphysis was 19.5%. The incidence of BMP-V and conical epiphysis was significantly (P<0.05) smaller in group A than in group B (11.1% vs. 23.8% for BMP-V and 16.6% vs. 25.2% for conical epiphysis, respectively). Additionally, 216 subjects were enrolled in group C (108 male and 108 female), 185 subjects were enrolled in in group D (93 male and 92 female), and 176 subjects were enrolled in in group E (104 male and 72 female). The second to fifth ESPs in group C were significantly (P<0.05) smaller than those in both groups D and E, while the second to fifth angles of the metacarpal-phalangeal axis were significantly (P<0.05) larger in group C than in both groups D and E. A BMP-V was present in 35 (16.2%) patients in group C, 8 (4.3%) in group D, and 2 (1.1%) in group E, and the difference among the three groups was statistically significant (P<0.05). Conclusions: The epiphyseal symmetry of the proximal phalanges is poor in short stature children and adolescents, and the angle between the metacarpal and phalangeal axes is larger in children and adolescents with short stature than those with normal height and good growth status. A negative correlation was found between the epiphyseal symmetry of the proximal phalanges and asymmetrical stress.

Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4.

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.

Efficacy of exclusive enteral nutrition on the mucosal healing of different gastrointestinal segments in children with Crohn's disease.

OBJECTIVE: To investigate the association between disease location and segmental mucosal healing (SMH) following exclusive enteral nutrition (EEN) in children with Crohn's disease (CD). METHODS: Treatment-naive pediatric patients with endoscopically active CD treated with EEN alone as induction therapy were retrospectively enrolled from January 1, 2017 to June 30, 2022. The simple endoscopic score for CD (SES-CD) was employed to score disease activity in the upper gastrointestinal (GI) tract (esophagus, stomach, duodenum), rectum, left colon, transverse colon, right colon, and terminal ileum. While the Lewis score assessed that of the small bowel from the jejunum to the proximal ileum (except the terminal ileum). The variation in the total scores for each segment and SES-CD subscores for each ileocolonic segment from baseline to 1 year after EEN therapy and the segmental endoscopic outcomes and potential predictors associated with SMH for the segments scored by SES-CD were evaluated. RESULTS: Overall, 82 children with CD were enrolled. Except for the upper GI segment, scores in other segments declined significantly from baseline to EEN completion (all P < 0.001). We analyzed 486 segments (79, 80, 81, 82, 82 and 82 from upper GI tract, terminal ileum, right colon, transverse colon, left colon, and rectum) and found that the segmental SES-CD at baseline (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.55-0.70, P < 0.001) and upper GI location (OR 0.25, 95% CI 0.11-0.55, P = 0.001) were associated with SMH at EEN completion. CONCLUSION: Disease location of the upper GI segment in pediatric CD was associated with SMH following EEN therapy.