Unilateral biportal endoscopy vs. open decompression for lumbar epidural lipomatosis-cohort study using a prospective registry.

Objective: This study aimed to compare the outcomes of unilateral biportal endoscopy, unilateral laminectomy bilateral decompression (UBE-ULBD), and open lumbar decompression (OLD) in patients with lumbar epidural lipomatosis (LEL). Methods: This prospective observational study was conducted from March 2019 to May 2022 and encompassed 33 patients with LEL who underwent lumbar decompression. The study included 15 cases of UBE-ULBD decompression and 18 cases of open decompression, which were followed up for 1 year. The baseline characteristics, initial clinical manifestations, and surgical details [including estimated blood loss (EBL) and preoperative complications] of all patients were recorded. Radiographic evaluation included the cross-sectional area (CSA) of the thecal sac and paraspinal muscles on MRI. Clinical results were analyzed using the Short Form-36 Score (SF-36), the Numeric Pain Rating Scale (NRS) for lumbar and leg pain, creatine kinase, the Roland and Morris Disability Questionnaire (RMDQ), and the Oswestry Disability Index (ODI). Results: The dural sac CSA increased considerably at the 1-year postoperative follow-up in both groups (p < 0.001). The operative duration in the OLD group (48.2 ± 7.2 min) was shorter than that in the UBE-ULBD group (67.7 ± 6.3 min, p < 0.001). The OLD group (97.2 ± 19.8 mL) was associated with more EBL than the UBE-ULBD group (40.6 ± 13.6 mL, p < 0.001). The duration of hospitalization in the OLD group (5.4 ± 1.3 days) was significantly longer compared with the UBE-ULBD group (3.5 ± 1.2 days, p < 0.01). The SF-36, NRS, RMDQ, and ODI scores improved in both groups postoperatively (p < 0.001). Serum creatine kinase values in the UBE-ULBD group (101.7 ± 15.5) were significantly lower than those in the OLD group (330.8 ± 28.1 U/L) 1 day after surgery (p < 0.001). The degree of paraspinal muscle atrophy in the UBE-ULBD group (4.81 ± 1.94) was significantly lower than that in the OLD group (12.15 ± 6.99) at 1 year (p < 0.001). Conclusion: UBE-ULBD and OLD demonstrated comparable clinical outcomes in treating LEL. However, UBE-ULBD surgery was associated with shorter hospital stays, lower rates of incision infection, lighter paravertebral muscle injury, and lower EBL than OLD surgery. Consequently, UBE-ULBD can be recommended in patients with LEL if conservative treatment fails.

An innovative label-free electrochemical aptamer sensor: utilizing Ti3C2Tx/MoS2/Au NPs for accurate interleukin-6 detection.

In the medical field, changes in interleukin-6 (IL-6) concentration serve as essential biomarkers for monitoring and diagnosing various conditions, including acute inflammatory responses such as those seen in trauma and burns, and chronic illnesses like cancer. This paper detailed a label-free electrochemical aptamer sensor designed for IL-6 quantification. A composite material consisting of Ti3C2Tx and MoS2 was successfully synthesized to fabricate this sensor. The synergistic effect of MoS2's catalytic action on hydrogen peroxide (H2O2), used as a signalling marker, when combined with the exceptional conductivity and large specific surface area of Ti3C2Tx, not only enables an increased loading of MoS2 but also significantly boosts the electrochemical response. The in situ-reduced Au NPs provided stable immobilization sites for DNA aptamers (DNAapt) and facilitated electron transfer, ensuring accurate IL-6 recognition. Under optimal conditions, the aptamer sensor exhibited a wide linear range (5 pg/mL to 100 ng/mL) and a low limit of detection (LOD) of 2.9 pg/mL. Its sensing performance in human serum samples highlights its potential as a promising clinical analysis tool.

Assessing the Feasibility of Simplifying the Scanning Protocol for Spinal Metastases With Vertebral Compression Fractures Using Only the Dixon T2-Weighted Sequence.

OBJECTIVE: Conventional imaging protocols, including sagittal T1-weighted imaging (T1WI) and water-only T2-weighted imaging (T2WI), are time consuming when screening for spinal metastases with vertebral compression fractures (VCFs). In this study, we aimed to assess the accuracy of using only the Dixon T2-weighted sequence in the diagnosis of spinal metastases with VCFs to determine its suitability as a simplified protocol for this task. METHODS: This retrospective study included 27 patients diagnosed with spinal metastases and VCFs. Qualitative analysis was performed separately by two musculoskeletal radiologists, who independently performed diagnostic evaluations of each vertebra using both conventional and simplified protocols. McNemar's test was then used to compare the differences in diagnostic results, and Cohen's kappa coefficient was used to assess interobserver and interprotocol agreement. Diagnostic performance values for both protocols, including sensitivity, specificity, and area under the curve, were then determined based on the reference standard. Quantitative image analysis was performed randomly for 30 metastases on T1WI and fat-only T2WI to measure the signal intensity, signal-to-noise ratio, and contrast-to-noise ratio. RESULTS: The diagnosis of VCFs by both radiologists was in full agreement with the reference standard. The classification of spinal metastases and diagnostic performance values determined by both radiologists were not significantly different between the two protocols (all P > 0.05), and the consistency between observers and protocols was excellent (κ = 0.973-0.991). The contrast-to-noise ratio of fat-only T2WI was significantly higher than that of T1WI (P < 0.001). CONCLUSIONS: The Dixon T2-weighted sequence alone performed well in diagnosing spinal metastases with VCFs, performing no worse than the conventional protocol (T1WI and water-only T2WI). This suggests that the Dixon T2-weighted sequence alone can serve as a simplified protocol for the diagnosis of spinal metastases with VCFs, thereby avoiding the need for more intricate scanning procedures.

A Patient Similarity Network (CHDmap) to Predict Outcomes After Congenital Heart Surgery: Development and Validation Study.

Background: Although evidence-based medicine proposes personalized care that considers the best evidence, it still fails to address personal treatment in many real clinical scenarios where the complexity of the situation makes none of the available evidence applicable. "Medicine-based evidence" (MBE), in which big data and machine learning techniques are embraced to derive treatment responses from appropriately matched patients in real-world clinical practice, was proposed. However, many challenges remain in translating this conceptual framework into practice. Objective: This study aimed to technically translate the MBE conceptual framework into practice and evaluate its performance in providing general decision support services for outcomes after congenital heart disease (CHD) surgery. Methods: Data from 4774 CHD surgeries were collected. A total of 66 indicators and all diagnoses were extracted from each echocardiographic report using natural language processing technology. Combined with some basic clinical and surgical information, the distances between each patient were measured by a series of calculation formulas. Inspired by structure-mapping theory, the fusion of distances between different dimensions can be modulated by clinical experts. In addition to supporting direct analogical reasoning, a machine learning model can be constructed based on similar patients to provide personalized prediction. A user-operable patient similarity network (PSN) of CHD called CHDmap was proposed and developed to provide general decision support services based on the MBE approach. Results: Using 256 CHD cases, CHDmap was evaluated on 2 different types of postoperative prognostic prediction tasks: a binary classification task to predict postoperative complications and a multiple classification task to predict mechanical ventilation duration. A simple poll of the k-most similar patients provided by the PSN can achieve better prediction results than the average performance of 3 clinicians. Constructing logistic regression models for prediction using similar patients obtained from the PSN can further improve the performance of the 2 tasks (best area under the receiver operating characteristic curve=0.810 and 0.926, respectively). With the support of CHDmap, clinicians substantially improved their predictive capabilities. Conclusions: Without individual optimization, CHDmap demonstrates competitive performance compared to clinical experts. In addition, CHDmap has the advantage of enabling clinicians to use their superior cognitive abilities in conjunction with it to make decisions that are sometimes even superior to those made using artificial intelligence models. The MBE approach can be embraced in clinical practice, and its full potential can be realized.

Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Mouse Corneal Epithelial Cells.

Purpose: Corneal epithelial homeostasis is maintained by coordinated gene expression across distinct cell populations, but the gene regulatory programs underlying this cellular diversity remain to be characterized. Here we applied single-cell multi-omics analysis to delineate the gene regulatory profile of mouse corneal epithelial cells under normal homeostasis. Methods: Single cells isolated from the cornea epithelium (with marginal conjunctiva) of adult mice were subjected to scRNA-seq and scATAC-seq using the 10×Genomics platform. Cell types were clustered by the graph-based visualization method uniform manifold approximation and projection and unbiased computational informatics analysis. The scRNA-seq and scATAC-seq datasets were integrated following the integration pipeline described in ArchR and Seurat. Results: We characterized diverse corneal epithelial cell types based on gene expression signatures and chromatin accessibility. We found that cell type-specific accessibility regions were mainly located at distal regions, suggesting essential roles of distal regulatory elements in determining corneal epithelial cell diversity. Trajectory analyses revealed a continuum of cell state transition and higher coordination between transcription factor (TF) motif accessibility and gene expression during corneal epithelial cell differentiation. By integrating transcriptomic and chromatin accessibility analysis, we identified cell type-specific and shared gene regulation programs. We also uncovered critical TFs driving corneal epithelial cell differentiation, such as nuclear factor I (NFI) family members, Rarg, Elf3. We found that nuclear factor-κB (NF-κB) family members were positive TFs in limbal cells and some superficial cells, but they were involved in regulating distinct biological processes. Conclusions: Our study presents a comprehensive gene regulatory landscape of mouse cornea epithelial cells, and provides valuable foundations for future investigation of corneal epithelial homeostasis in the context of cornea pathologies and regenerative medicine.

The Mechanism of Houttuynia cordata Embryotoxicity Was Explored in Combination with an Experimental Model and Network Pharmacology.

Houttuynia cordata (H. cordata) is the most common herb as a food and traditional Chinese medicine. Currently, studies on its toxicity have mainly focused on hepatotoxicity. However, its potential embryotoxicity by long-term exposure is often overlooked. Objective: To investigate the effects of H. cordata on embryonic development and its toxicity mechanism by combining network pharmacology, molecular docking, and in vitro experimental methods. Methods: The effects of H. cordata on embryos were evaluated. Zebrafish embryos and embryoid bodies were administered to observe the effects of H. cordata on embryonic development. Based on network pharmacological analysis, it was found that the main active agents producing toxicity in H. cordata were oleanolic acid, lignan, and aristolactam AII. H. cordata can affect PI3K-Akt, MAPK, and Ras signaling pathways by regulating targets, such as AKT1, EGFR, CASP3, and IGF-1. RT-PCR and immunohistochemistry results showed that the expression of AKT1 and PI3K in the embryoid body was significantly reduced after drug administration (p < 0.05). Conclusions: The results of network pharmacology and in vitro experiments suggest that H. cordata may affect embryonic development by influencing the PI3K-Akt signaling pathway.

Predicting pathological complete response of neoadjuvant radiotherapy and targeted therapy for soft tissue sarcoma by whole-tumor texture analysis of multisequence MRI imaging.

OBJECTIVES: To construct effective prediction models for neoadjuvant radiotherapy (RT) and targeted therapy based on whole-tumor texture analysis of multisequence MRI for soft tissue sarcoma (STS) patients. METHODS: Thirty patients with STS of the extremities or trunk from a prospective phase II trial were enrolled for this analysis. All patients underwent pre- and post-neoadjuvant RT MRI examinations from which whole-tumor texture features were extracted, including T1-weighted with fat saturation and contrast enhancement (T1FSGd), T2-weighted with fat saturation (T2FS), and diffusion-weighted imaging (DWI) sequences and their corresponding apparent diffusion coefficient (ADC) maps. According to the postoperative pathological results, the patients were divided into pathological complete response (pCR) and non-pCR (N-pCR) groups. pCR was defined as less than 5% of residual tumor cells by postoperative pathology. Delta features were defined as the percentage change in a texture feature from pre- to post-neoadjuvant RT MRI. After data reduction and feature selection, logistic regression was used to build prediction models. ROC analysis was performed to assess the diagnostic performance. RESULTS: Five of 30 patients (16.7%) achieved pCR. The Delta_Model (AUC 0.92) had a better predictive ability than the Pre_Model (AUC 0.78) and Post_Model (AUC 0.76) and was better than AJCC staging (AUC 0.52) and RECIST 1.1 criteria (AUC 0.52). The Combined_Model (pre, post, and delta features) had the best predictive performance (AUC 0.95). CONCLUSION: Whole-tumor texture analysis of multisequence MRI can well predict pCR status after neoadjuvant RT and targeted therapy in STS patients, with better performance than RECIST 1.1 and AJCC staging. KEY POINTS: • MRI multisequence texture analysis could predict the efficacy of neoadjuvant RT and targeted therapy for STS patients. • Texture features showed incremental value beyond routine clinical factors. • The Combined_Model with features at multiple time points showed the best performance.

Landscape of DILI-related adverse drug reaction in China Mainland.

Drug-induced liver injury (DILI) is a type of bizarre adverse drug reaction (ADR) damaging liver (L-ADR) which may lead to substantial hospitalizations and mortality. Due to the general low incidence, detection of L-ADR remains an unsolved public health challenge. Therefore, we used the data of 6.673 million of ADR reports from January 1st, 2012 to December 31st, 2016 in China National ADR Monitoring System to establish a new database of L-ADR reports for future investigation. Results showed that totally 114,357 ADR reports were retrieved by keywords searching of liver-related injuries from the original heterogeneous system. By cleaning and standardizing the data fields by the dictionary of synonyms and English translation, we resulted 94,593 ADR records reported to liver injury and then created a new database ready for computer mining. The reporting status of L-ADR showed a persistent 1.62-fold change over the past five years. The national population-adjusted reporting numbers of L-ADR manifested an upward trend with age increasing and more evident in men. The annual reporting rate of L-ADR in age group over 80 years old strikingly exceeded the annual DILI incidence rate in general population, despite known underreporting situation in spontaneous ADR reporting system. The percentage of herbal and traditional medicines (H/TM) L-ADR reports in the whole number was 4.5%, while 80.60% of the H/TM reports were new findings. There was great geographical disparity of reported agents, i.e. more cardiovascular and antineoplastic agents were reported in higher socio-demographic index (SDI) regions and more antimicrobials, especially antitubercular agents, were reported in lower SDI regions. In conclusion, this study presented a large-scale, unbiased, unified, and computer-minable L-ADR database for further investigation. Age-, sex- and SDI-related risks of L-ADR incidence warrant to emphasize the precise pharmacovigilance policies within China or other regions in the world.

Osteofibrous dysplasia-like adamantinoma: A case report and literature review.

Abstract background: Osteofibrous dysplasia-like adamantinoma (OFD-like adamantinoma), classical adamantinoma and dedifferentiated adamantinoma were previously considered to be three subtypes of adamantinoma of long bones. In the 5th edition of the World Health Organization (WHO) classification of bone tumors in 2020, OFD-like adamantinoma was newly proposed and classified as an intermediate-locally aggressive tumor in other mesenchymal tumors of bone. OFD-like adamantinoma is rare, accounting for only 0.4% of all primary bone tumors. OFD-like adamantinoma is often misdiagnosed due to the insufficient understanding of it. Here we report a case of OFD-like adamantinoma treated in our hospital with a literature review. Case presentation: The patient, a 14-year-old male, had swelling in his right leg with intermittent pain for one year. Plain radiography, computed tomography (CT) and magnetic resonance imaging (MRI) were performed. Based on the radiological and histological examinations, a diagnosis of OFD-like adamantinoma was suspected. After admission, the patient underwent tumor resection of the right tibia, free transplantation of the left fibula and internal fixation. After resection of the tumor, the wound recovered well, the vital signs were stable, and activity was normal. The patient has been followed up for more than a year with no recurrence or distant metastasis. Conclusion: OFD-like adamantinoma is a rare primary bone tumor with nonspecific clinical features. Imaging examination can demonstrate the lesion and help diagnosis. The pathological discovery of epithelioid tissue is the key evidence for diagnosis.

Recent advances in the intracellular delivery of macromolecule therapeutics.

Intracellular delivery of macromolecules is a critical procedure for biological research and drug discovery, including proteins, peptides, vaccines, antibodies and genes. The penetration of macromolecule therapeutics through the cell membrane to intracellular targets is a prerequisite for their biological activity, but most delivery systems rely on the endocytic pathway to enter the cell and confront an inability to escape from the lysosome. A profound understanding of the cellular internalization of transporting carriers can (i) optimize the design of drug delivery systems, (ii) maintain the biological activity of biomolecular drugs, (iii) improve the efficiency of intracellular macromolecule transport and release, (iv) bring new opportunities for the discovery of macromolecule therapeutics and treatment of refractory disease. This article summarizes the uptake pathway of intracellular delivery vehicles for macromolecule drugs, hoping to provide ideas and references for macromolecule therapeutics delivery systems.

Efficacy evaluation of contrast-enhanced magnetic resonance imaging in differentiating glioma from metastatic tumor of the brain and exploration of its association with patients' neurological function.

Objective: To determine the efficacy of contrast-enhanced MRI in differentiating glioma (GL) from the metastatic tumor of the brain (MTB) and its association with patients' neurological function. Methods: A retrospective analysis was conducted on 49 cases of pathologically confirmed GL and 42 cases of MTB admitted between April 2019 and January 2022. All patients were examined by a set of MRI sequences that included T1WI, T2WI, FLAIR, and DWI. The values of fractional anisotropy (FA), apparent diffusion coefficient (ADC), and operation coefficient (Ktrans) were calculated by taking the tumor parenchyma area, cystic area, and peritumor edema area as the regions of interest (ROIs). And according to the Mini-mental state examination (MMSE) results, the contrast-enhanced MRI with patients' neurological dysfunction was observed. Results: The clinical symptoms and MRI findings of MTB and GL were basically the same, mainly showing neurological symptoms. The tumor parenchyma area and cystic area were mainly located in the tumor periphery and tumor central area, respectively, while the peritumor edema area was widely distributed, showing an irregular patchy edema zone. Contrast-enhanced scans suggested an obvious enhancement in the tumor parenchymal area, presenting with nodular and annular enhancement, but no enhancement in the tumor cystic and peritumor edema areas. There was no difference between GL and MTB in FA values of tumor cystic area and peritumor edema area (P > 0.05), but the FA value of the parenchyma area of GL was higher (P < 0.05). Besides, GL and MTB showed no difference in ADC and Ktrans values (P > 0.05), while the former presented lower ADC values and higher Ktrans values of the peritumor edema area than the latter (P < 0.05). In patients with GL and MTB, the FA and Ktrans values of all ROIs in those with neurological dysfunction were higher compared with those without neurological dysfunction, while the ADC values were lower (P < 0.05). Conclusion: Contrast-enhanced MRI of peritumor edema area can effectively distinguish GL from MTB, and improve the accuracy of early clinical screening, thus providing more reliable life security for patients.

Biocompatible Au-Fe3O4 Nanoparticle-based Magnetic Resonance Imaging in the Diagnosis of Liver Tumor.

The study aimed to analyze the value and significance of magnetic resonance imaging (MRI) using biocompatible Au-Fe3O4 nanomaterials in the diagnosis of liver tumors. In this study, 124 patients with liver tumors were selected to perform MRI scanning based on Au-Fe3O4 nanoparticles. The coincidence rate between MRI scanning results and pathological examination results, the detection rate of tumor focus between MRI scanning results and CT detection results were analyzed, to evaluate the diagnostic performance of MRI scanning based on Au-Fe3O4 nanoparticles. The results showed that in the detection of primary tumors, secondary tumors, and focal nodular hyperplasia, the coincidence rate between MRI scanning results and pathological examination results was high, and Kappa values were all greater than 0.8. Compared with the results of CT, the detection rate of tumor lesions smaller than 1 cm by MRI was significantly higher (P<0.05), but there was no significant difference between the two diagnostic methods for tumor lesions larger than 1 cm (P>0.05). Additionally, the accuracy, specificity, and sensitivity of MRI in diagnosing liver tumors were 86.81, 84.29, and 77.27, respectively. Clinically, MRI scanning based on Au-Fe3O4nanoparticles can provide a practical and effective reference for the differential diagnosis of liver tumors.

Two Children With Steroid-Resistant Significant Proteinuria Due to Nonsense Mutations of the TRIM8 Gene: A Case Report and Literature Review.

Background: TRIM8 gene mutations have been reported as the genetic basis of autosomal dominant (AD) neuro-renal syndrome in children, which presents with epileptic encephalopathy, focal segmental glomerulosclerosis (FSGS), developmental delay, and mental retardation. In this study, we report the cases of two children with significant proteinuria due to de novo nonsense mutations of the TRIM8 gene. Case Presentation: Case 1 was a 7-year-old girl who presented with proteinuria and developmental delay, and her renal biopsy showed FSGS. She developed end-stage renal disease (ESRD) 3 years after onset. Case 2 was another 7-year-old girl who developed proteinuria only at age 3, and renal biopsy showed glomerular segmental mesangial proliferative lesions. The two girls underwent genetic testing but we did not find a positive result in the whole exon. However, cluster analysis revealed two new nonsense mutations of the TRIM8 gene (c.1461C>A, p.Tyr 487* and c.1453C>T, p.Gln485*). Conclusions: We reported the clinical manifestation of this neuro-renal syndrome for the first time in China. It is necessary to perform genetic testing in children with steroid-resistant significant proteinuria to identify its etiology and avoid the side effects of immunosuppressants.

Adapalene Inhibits Prostate Cancer Cell Proliferation In Vitro and In Vivo by Inducing DNA Damage, S-phase Cell Cycle Arrest, and Apoptosis.

Aims: Prostate cancer is a well-known aggressive malignant tumor in men with a high metastasis rate and poor prognosis. Adapalene (ADA) is a third-generation synthetic retinoid with anticancer properties. We investigated the anti-tumor activity and molecular mechanisms of ADA in the RM-1 prostate cancer cell line in vivo and in vitro. Methods: The effects of ADA on cell proliferation were estimated using the CCK-8 and colony formation assays. The wound-healing assay and the Transwell assay were employed to examine the migratory capacity and invasiveness of the cells. Flow cytometry was utilized to evaluate the cell cycle and apoptosis, and Western blotting analysis was used to assess the expression of the associated proteins. Micro-CT, histomorphological, and immunohistochemical staining were used to assess the effects of ADA on bone tissue structure and tumor growth in a mouse model of prostate cancer bone metastasis. Result: ADA dramatically inhibited cell proliferation, migration, invasiveness, and induced S-phase arrest and apoptosis. ADA also regulated the expression of S-phase associated proteins and elevated the levels of DNA damage markers, p53, and p21 after ADA treatment, suggesting that the anti-tumor effect of ADA manifests through the DNA damage/p53 pathway. Furthermore, we observed that ADA could effectively inhibited tumor growth and bone destruction in mice. Conclusion: ADA inhibited prostate cancer cell proliferation, elicited apoptosis, and arrested the cell cycle in the S-phase. ADA also slowed the rate of tumor growth and bone destruction in vitro. Overall, our results suggest that ADA may be a potential treatment against prostate cancer.

Boosting oxygen evolution by nickel nitrate hydroxide with abundant grain boundaries via segregated high-valence molybdenum.

High-valence metal doping and abundant grain boundaries (GBs) have been proved to be effective strategies to promote the oxygen evolution reaction (OER). However, the reasonable design of the two to facilitate OER collaboratively is challenging. Herein, a convenient and novel one-step molten salt decomposition strategy is proposed to fabricate segregated-Mo doped nickle nitrate hydroxide with substantial GBs on MoNi foam (Mo-NNOH@MNF). When processed in molten salt, the Mo species on the conductive substrate migrates unevenly to the surface of Mo-NNOH@MNF, which not only induces the formation of abundant GBs to modulate electronic structure, but also improves the intrinsic activity as high-valence dopants, synergistically elevating OER activity. As verification, the optimized Mo-NNOH@MNF-10h exhibits low overpotential of 150 mV at 10 mA cm-2, which can be attributed to the reduced valence charge transition energy of Ni by high-valence Mo dopant, coupled with the fine-tuning of d-band center bond and corresponding local electron density by induced GBs and Mo doping, as DFT calculations revealed. Moreover, the intrinsic robustness and strong adhesion ensure the long-term stability of 6 h at 500 mA cm-2. This work provides a promising molten salt decomposition approach to synthesize advanced materials with unique structures.

Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. AIM OF THE STUDY: To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. MATERIALS AND METHODS: Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1ß, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. RESULTS: Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1ß, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. CONCLUSION: These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases.

Analysis and comparison of failure causes of minimally invasive surgical closure of ventricular septal defects in children.

Objectives: The aims of the present study were to explore the causes of minimally invasive surgical ventricular septal defect (VSD) closure failure under transesophageal echocardiography guidance and thus to improve the success rate of surgical VSD closure. Methods: From January 2015 to December 2019, 522 children with VSD underwent minimally invasive surgical closure. Nineteen procedures (3.64%) were unsuccessful. The failure causes, VSD locations and surgical incision approaches were retrospectively analyzed. Results: Among the 19 patients (3.64%) with unsuccessful outcomes, 18 were switched to cardiopulmonary bypass (CPB) surgery, and 1 was closed successfully using an occlusion device a year later. The causes of failure included occlusion device shedding or shifting (n=6), failure of the guidewire (or the sheath) to pass through a small defect (n=5), device-related valve regurgitation (n=4), significant residual shunt (n=2), ventricular fibrillation (n=1), and continuous sharp blood pressure decreases (n=1). Patients with high VSD had a slightly higher failure rate than those with perimembranous VSD (p=0.049), and its key reason is the high proportion of occlusion device shedding or shifting (p=0.001). No significant difference in the failure rate was found between patients with different surgical incision approaches. Conclusions: Minimally invasive surgery has a high success rate for perimembranous VSDs. Occlusion device shedding or shifting is the most common cause of failure. The shedding or shifting risk of eccentric occlusion devices being used only for high VSDs is much greater than that of concentric occlusion devices being used for perimembranous VSDs, which increases the risk of conversion to CPB surgery for high VSDs.

Clinical and imaging features of desmoid tumors of the extremities.

BACKGROUND: Desmoid fibroma is a rare soft tissue tumor originating from the aponeurosis, fascia, and muscle, and it is also known as aponeurotic fibroma, invasive fibroma, or ligamentous fibroma. AIM: To investigate the clinical and imaging features of desmoid tumors of the extremities. METHODS: Thirteen patients with desmoid fibroma of the extremities admitted to our hospital from October 2016 to March 2021 were included. All patients underwent computed tomography (CT), magnetic resonance imaging (MRI), and pathological examination of the lesion. Data on the diameter and distribution of the lesion, the relationship between the lesion morphology and surrounding structures, MRI and CT findings, and pathological features were statistically analyzed. RESULTS: The lesion diameter ranged from 1.7 to 8.9 cm, with an average of 5.35 ± 2.39 cm. All lesions were located in the deep muscular space, with the left and right forearm each accounting for 23.08% of cases. Among the 13 patients with desmoid fibroma of the extremities, the lesions were "patchy" in 1 case, irregular in 10, and quasi-round in 2. The boundary between the lesion and surrounding soft tissue was blurred in 10 cases, and the focus infiltrated along the tissue space and invaded the adjacent structures. Furthermore, the edge of the lesion showed "beard-like" infiltration in 2 cases; bone resorption and damage were found in 8, and bending of the bone was present in 2; the boundary of the focus was clear in 1. According to the MRI examination, the lesions were larger than 5 cm (61.54%), round or fusiform in shape (84.62%), had an unclear boundary (76.92%), showed uniform signal (69.23%), inhomogeneous enhancement (84.62%), and "root" or "claw" infiltration (69.23%). Neurovascular tract invasion was present in 30.77% of cases. CT examination showed that the desmoid tumors had slightly a lower density (69.23%), higher enhancement (61.54%), and unclear boundary (84.62%); a CT value < 50 Hu was present in 53.85% of lesions, and the enhancement was uneven in 53.85% of cases. Microscopically, fibroblasts and myofibroblasts were arranged in strands and bundles, without obvious atypia but with occasional karyotyping; cells were surrounded by collagen tissue. There were disparities in the proportion of collagen tissue in different regions, with abundant collagen tissue and few tumor cells in some areas, similar to the structure of aponeuroses or ligaments, and tumor cells invading the surrounding tissues. CONCLUSION: Desmoid tumors of the extremities have certain imaging features on CT and MRI. The two imaging techniques can be combined to improve the diagnostic accuracy, achieve a comprehensive diagnosis of the disease in the clinical practice, and reduce the risk of missed diagnosis or misdiagnosis. In addition, their use can ensure timely diagnosis and treatment.

Preoperative volumetric synthetic magnetic resonance imaging of the primary tumor for a more accurate prediction of lymph node metastasis in rectal cancer.

BACKGROUND: An accurate assessment of lymph node (LN) status in patients with rectal cancer is important for treatment planning and an essential factor for predicting local recurrence and overall survival. In this study, we explored the potential value of histogram parameters of synthetic magnetic resonance imaging (SyMRI) in predicting LN metastasis in rectal cancer and compared their predictive performance with traditional morphological characteristics and chemical shift effect (CSE). METHODS: A total of 70 patients with pathologically proven rectal adenocarcinoma who received direct surgical resection were enrolled in this prospective study. Preoperative rectal MRI, including SyMRI, were performed, and morphological characteristics and CSE of LN were assessed. Histogram parameters were extracted on a T1 map, T2 map, and proton density (PD) map, including mean, variance, maximum, minimum, 10th percentile, median, 90th percentile, energy, kurtosis, entropy, and skewness. Receiver operating characteristic (ROC) curves were used to explore their predictive performance for assessing LN status. RESULTS: Significant differences in the energy of the T1, T2, and PD maps were observed between LN-negative and LN-positive groups [all P<0.001; the area under the ROC curve (AUC) was 0.838, 0.858, and 0.823, respectively]. The maximum and kurtosis of the T2 map, maximum, and variance of PD map could also predict LN metastasis with moderate diagnostic power (P=0.032, 0.045, 0.016, and 0.047, respectively). Energy of the T1 map [odds ratio (OR) =1.683, 95% confidence interval (CI): 1.207-2.346, P=0.002] and extramural venous invasion on MRI (mrEMVI) (OR =10.853, 95% CI: 2.339-50.364, P=0.002) were significant predictors of LN metastasis. Moreover, the T1 map energy significantly improved the predictive performance compared to morphological features and CSE (P=0.0002 and 0.0485). CONCLUSIONS: The histogram parameters derived from SyMRI of the primary tumor were associated with LN metastasis in rectal cancer and could significantly improve the predictive performance compared with morphological features and CSE.