Overexpressed miR-486 in bone marrow mesenchymal stem cells represses urethral fibrosis and targets Col13a1 in urethral stricture rats.

Urethral stricture (US) is a challenging problem in urology and its pathogenesis of US is closely related to the fibrotic process. Previous evidence has indicated the downregulation of microRNA (miR)-486 in injured urethral specimens of rats. This study aimed to explore the effects of miR-486-overexpressed bone marrow mesenchymal stem cells (BMSCs) on US. BMSCs were identified by detecting their multipotency and surface antigens. Lentivirus virus expressing miR-486 was transduced into rat BMSCs to overexpress miR-486. Transforming growth factor (TGF)-ß1 induced fibrotic phenotypes in urethral fibroblasts (UFs) and rat models. Western blotting showed protein levels of collagen I/III and collagen type XIII alpha 1 chain (Col13a1). Real time quantitative polymerase chain reaction was utilized for messenger RNA level evaluation. Hematoxylin-eosin, Masson's trichrome, and Von Willebrand Factor staining were conducted for histopathological analysis. Immunofluorescence staining was employed for detecting alpha smooth muscle actin (α-SMA) expression. Luciferase reporter assay verified the interaction between miR-486 and Col13a1. The results showed that miR-486-overexpressed BMSCs suppressed collagen I/III and α-SMA expression in TGF-ß1-stimulated UFs. miR-486-overexpressed BMSCs alleviated urethral fibrosis, collagen deposition, and epithelial injury in the urethral tissue of US rats. miR-486 targeted and negatively regulated Col13a1 in US rats. In conclusion, overexpression of miR-486 in BMSCs targets Col13a1 and attenuates urethral fibrosis in TGF-ß1-triggered UFs and US rats.

Combination of microwave ablation and systemic treatments achieve a long survival time for a patient with metachronous advanced double primary lung and colon adenocarcinoma: A case report.

Despite significant improvements that have been made in terms of progression-free survival and overall survival rates brought about by targeted therapy in non-small cell lung cancer (NSCLC), the emergence of drug resistance remains a limiting factor. However, a previous study has shown promising results by combining local microwave ablation (MWA) with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy for patients with oligometastatic NSCLC. The current study presented the case of a Chinese female patient who was identified as having lung adenocarcinoma (LADC) with EGFR exon 19 deletions (Del) in January 2014, and who experienced multiple instances of oligoprogression but showed a positive response to a combination of chemotherapy, MWA and a TKI drug. First, the patient was treated with four cycles of chemotherapy (120 mg docetaxel on day 1 and 40 mg cisplatin on days 1, 2 and 3; every three weeks as one cycle) and gefitinib (Iressa; 250 mg/day), maintaining a partial response for 17 months. In August 2015, a new solitary lesion was identified in the right lung and erlotinib (Tarceva; 150 mg/day) was administered for 3 months thereafter. In response, the patient underwent ablation of both the new right lung lesion and the primary left lung lesion in January 2016. Subsequently, a treatment course consisting of six cycles of chemotherapy (0.8 g pemetrexed on day 1 and 70 mg nedaplatin on days 1 and 2; every three weeks as one cycle) resulted in stable disease. In May 2016, the patient began treatment with osimertinib (AZD9291; 80 mg/day), resulting in a rapid shrinkage of the mediastinal lymph node after one month, which has been providing a benefit for the patient for 82 months and counting. Of note, the patient also developed metachronous colon cancer in January 2020, followed by the identification of right posterior liver metastases in February 2020 and lung metastases in May 2021 and in February 2022. To address this, the patient underwent radical resection of colon cancer and liver metastasectomy and received a combination of chemotherapy with bevacizumab, along with MWA for lung metastases. Remarkably, the patient has achieved long-term survival of 110 months. In conclusion, this case highlights the promising potential of combining MWA with systemic therapy for a patient with advanced LADC harboring EGFR exon 19 Del and metachronous lung and liver-metastasized colon adenocarcinoma. MWA effectively controlled both in situ oligoprogression and new oligoprogression, thereby enhancing the efficacy of systematic chemotherapy/TKI therapy. Furthermore, this case report emphasizes the importance of repeated histologic biopsies and genetic testing as reliable indicators for adjusting treatment regimens. Physicians should also remain vigilant regarding the occurrence of secondary primary carcinomas, and timely and accurate adjustments to treatment plans will be of significant benefit to patients in terms of treatment efficacy and overall quality of life.

Common endocrine system adverse events associated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs), a novel anti-tumor therapeutic modality, are monoclonal antibodies targeting certain immune checkpoints (ICs) that reactivate T cells to achieve anti-tumor immunity by targeting, binding, and blocking ICs. Targeted inhibitory antibodies against the ICs cytotoxic T-lymphocyte antigen and programmed death receptor-1 have demonstrated efficacy and durable anti-tumor activity in patients with cancer. ICs may prevent autoimmune reactions. However, ICIs may disrupt ICs properties and trigger autoimmune-related adverse reactions involving various organ systems including the cardiovascular, pulmonary, gastrointestinal, renal, musculoskeletal, dermal, and endocrine systems. Approximately 10% of patients with damage to target organs such as the thyroid, pituitary, pancreas, and adrenal glands develop endocrine system immune-related adverse events (irAEs) such as thyroid dysfunction, pituitary gland inflammation, diabetes mellitus, and primary adrenal insufficiency. However, the symptoms of immunotherapy-associated endocrine system irAEs may be nonspecific and similar to those of other treatment-related adverse reactions, and failure to recognize them early may lead to death. Timely detection and treatment of immunotherapy-associated endocrine irAEs is essential to improve the efficacy of immunotherapy, prognosis, and the quality of life of patients. This study aimed to review the mechanisms by which ICIs cause endocrine irAEs providing guidance for the development of appropriate management protocols. Here, we discuss (1) the biological mechanisms of ICs in tumorigenesis and progression, focusing on cytotoxic T-lymphocyte antigen and programmed cell death-1/programmed cell death-ligand 1; and (2) the epidemiology, clinical symptoms, diagnosis, and treatment of four immunotherapy-related endocrine complications.

Two cases of atrial myxoma with calcification and ossification as the main features.

BACKGROUND: Cardiac myxomas are the most common type of primary cardiac tumors in adults, but they can have variable features that make them difficult to diagnose. We report two cases of atrial myxoma with calcification or ossification, which are rare pathological subgroups of myxoma. CASE PRESENTATION: A 47-year-old woman and a 35-year-old man presented to our hospital with different symptoms. Both patients had a history of chronic diseases. Transthoracic and transesophageal echocardiography revealed a mass in the left or right atrium, respectively, with strong echogenicity and echogenic shadows. The masses were suspected to be malignant tumors with calcification or ossification. Contrast transthoracic echocardiography(cTEE) showed low blood supply within the lesions. The patients underwent surgical resection of the atrial mass, and the pathology confirmed myxoma with partial ossification or massive calcification. CONCLUSION: We report two rare cases of atrial myxoma with calcification or ossification and analyze their ultrasonographic features. Transthoracic echocardiography and cTEE can provide valuable information for the diagnosis and management of such mass. However, distinguishing calcification and ossification in myxoma from calcification in malignant tumors is challenging. More studies are needed to understand the pathogenesis and imaging characteristics of these myxoma variants.

Plasma metals, genetic risk, and rapid kidney function decline among type 2 diabetes.

BACKGROUND: Rapid kidney function decline (RKFD) is a main clinical feature of early chronic kidney disease (CKD) in type 2 diabetes (T2D). Environmental and genetic factors influencing RKFD remain inadequately elucidated. OBJECTIVES: This study aimed to examine the associations of metals with RKFD among T2D and to further investigate the effect of metal mixtures on RKFD with the modifying effect of genetic susceptibility. METHODS: This study included 2209 people with T2D (1942 had genotyping data) free of CKD at baseline from the Dongfeng-Tongji cohort. We used inductively coupled plasma-mass spectrometry (ICP-MS) to measure 23 metals in baseline plasma. Using elastic net (ENET), multivariate logistic regression, and Bayesian kernel machine regression (BKMR) model, we examined independent associations of multiple metals with RKFD. We calculated the environmental risk score (ERS) to assess the effects of metal mixtures on RKFD and the genetic risk score (GRS) to assess genetic susceptibility. RKFD was defined as estimated glomerular filtration rate (eGFR) loss > 3 mL/min/1.73 m2/year. RESULTS: During a median of 9.8 years follow-up, 262 participants developed RKFD. Aluminum, vanadium, zinc, selenium, rubidium, tin, barium, and tungsten were screened from ENET. In multivariate logistic models, vanadium, selenium, and tungsten were negatively associated with RKFD, while zinc, tin, and rubidium were positively associated. The BKMR showed a nonlinear association of vanadium and rubidium with RKFD and interactions between metals (barium­vanadium, barium­rubidium). The ERS was positive associated with RKFD (per SD increase in ERS, OR = 1.94, 95% CI: 1.66, 2.27). No significant interaction between ERS and GRS was observed on RKFD, however, participants in the highest ERS and GRS group had the highest RKFD risk. CONCLUSION: Vanadium and rubidium were associated with RKFD in T2D. Metal mixtures was associated with an increased risk of RKFD in T2D, particularly in those at high genetic risk.

Red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain through stimulating the expressions of TNF-α and IL-1ß.

Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors (mGluR). Here, we further explored the actions and possible molecular mechanisms of red nucleus mGluR Ⅰ (mGluR1 and mGluR5) in the development of neuropathic pain induced by spared nerve injury (SNI). Our data indicated that both mGluR1 and mGluR5 were constitutively expressed in the RN of normal rats. Two weeks after SNI, the expressions of mGluR1 and mGluR5 were significantly boosted in the RN contralateral to the nerve injury. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN contralateral to the nerve injury at 2 weeks post-SNI significantly ameliorated SNI-induced neuropathic pain. However, unilateral administration of mGluRⅠ agonist DHPG to the RN of normal rats provoked a significant mechanical allodynia, this effect could be blocked by LY367385 or MTEP. Further studies indicated that the expressions of TNF-α and IL-1ß in the RN were also elevated at 2 weeks post-SNI. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN at 2 weeks post-SNI significantly inhibited the elevations of TNF-α and IL-1ß. However, administration of mGluR Ⅰ agonist DHPG to the RN of normal rats significantly enhanced the expressions of TNF-α and IL-1ß, these effects were blocked by LY367385 or MTEP. These results suggest that activation of red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain by stimulating the expressions of TNF-α and IL-1ß. mGluR Ⅰ maybe potential targets for drug development and clinical treatment of neuropathic pain.

Predictive value of bronchoscopy combined with CT score for refractory mycoplasma pneumoniae pneumonia in children.

INTRODUCTION: Mycoplasma pneumoniae pneumonia (MPP) is prevalent in paediatric patients and can progress to refractory mycoplasma pneumoniae pneumonia (RMPP). OBJECTIVE: To assess the predictive value of bronchoscopy combined with computed tomography (CT) score in identifying RMPP in children. METHODS: A retrospective analysis was conducted on 244 paediatric patients with MP, categorising them into RMPP and general mycoplasma pneumoniae pneumonia (GMPP) groups. A paired t-test compared the bronchitis score (BS) and CT score before and after treatment, supplemented by receiver operating characteristic (ROC) analysis. RESULTS: The RMPP group showed higher incidences of extrapulmonary complications and pleural effusion (58.10% and 40%, respectively) compared with the GMPP group (44.60%, p = 0.037 and 18.71%, p < 0.001, respectively). The CT scores for each lung lobe were statistically significant between the groups, except for the right upper lobe (p < 0.05). Correlation analysis between the total CT score and total BS yielded r = 0.346 and p < 0.001. The ROC for BS combined with CT score, including area under the curve, sensitivity, specificity, and cut-off values, were 0.82, 0.89, 0.64, and 0.53, respectively. CONCLUSION: The combined BS and CT score method is highly valuable in identifying RMPP in children.

The positive impact of smoking on poor sleep quality is moderated by IGF1 levels in cerebrospinal fluid: a case-control study among Chinese adults.

Objective: Previous research indicates associations between cigarette smoking, insulin-like growth factor-1 (IGF1), and sleep disturbances. This study aimed to examine the association between smoking and sleep quality and investigate the moderating role of IGF1. Methods: This case-control study involved 146 Chinese adult males (53 active smokers and 93 non-smokers) from September 2014 to January 2016. Sleep quality and disturbances were evaluated using the Pittsburgh Sleep Quality Index (PSQI), which includes seven scales. Pearson correlation analysis and logistic regression analysis were utilized to examine the link between IGF1 levels in cerebrospinal fluid (CSF) and PSQI scores. The effect of IGF1 was assessed using the moderation effect and simple slope analysis, with adjustments made for potential confounders. Results: Active smokers exhibited significantly higher global PSQI scores and lower IGF1 levels in CSF compared to non-smokers. A significant negative correlation was observed between IGF1 and PSQI scores (â = -0.28, P < 0.001), with a stronger association in non-smokers (Pearson r = -0.30) compared to smokers (Pearson r = -0.01). Smoking was associated with higher global PSQI scores (â = 0.282, P < 0.001), and this association was moderated by IGF1 levels in CSF (â = 0.145, P < 0.05), with a stronger effect at high IGF1 levels (Bsimple = 0.402, p < 0.001) compared to low IGF1 levels (Bsimple = 0.112, p = 0.268). Four subgroup analysis revealed similar results for sleep disturbances (Bsimple = 0.628, P < 0.001), with a marginal moderation effect observed on subjective sleep quality (Bsimple = 0.150, P = 0.070). However, independent associations rather than moderating effects were observed between IGF1 and sleep efficiency and daytime disturbance. Conclusion: We provided evidence to demonstrate the moderation effect of IGF1 on the relationship between smoking and sleep in CSF among Chinese adult males.

Hyaluronic Acid Interacting Molecules Mediated Crosstalk between Cancer Cells and Microenvironment from Primary Tumour to Distant Metastasis.

Hyaluronic acid (HA) is a prominent component of the extracellular matrix, and its interactions with HA-interacting molecules (HAIMs) play a critical role in cancer development and disease progression. This review explores the multifaceted role of HAIMs in the context of cancer, focusing on their influence on disease progression by dissecting relevant cellular and molecular mechanisms in tumour cells and the tumour microenvironment. Cancer progression can be profoundly affected by the interactions between HA and HAIMs. They modulate critical processes such as cell adhesion, migration, invasion, and proliferation. The TME serves as a dynamic platform in which HAIMs contribute to the formation of a unique niche. The resulting changes in HA composition profoundly influence the biophysical properties of the TME. These modifications in the TME, in conjunction with HAIMs, impact angiogenesis, immune cell recruitment, and immune evasion. Therefore, understanding the intricate interplay between HAIMs and HA within the cancer context is essential for developing novel therapeutic strategies. Targeting these interactions offers promising avenues for cancer treatment, as they hold the potential to disrupt critical aspects of disease progression and the TME. Further research in this field is imperative for advancing our knowledge and the treatment of cancer.

Application of Human Acellular Dermal Matrix with Skin Graft for Lacunar Soft-Tissue Defect of Lateral Heel after Calcaneal Fracture.

OBJECTIVE: To investigate the clinical effect of human acellular dermal matrix (HADM) combined with split-thickness skin graft in repairing lacunar soft tissue defects of the lateral heel after calcaneal fracture. METHODS: From June 2018 to October 2020, providers repaired 11 cases of lacunar soft tissue defects at the lateral part of the heel using HADM combined with split-thickness skin graft. After thorough debridement, the HADM was trimmed and filled into the lacunar defect area. Once the wound was covered, a split-thickness skin graft and negative-pressure wound therapy were applied. Providers evaluated the appearance, scar, ductility of the skin graft site, appearance of the donor site, healing time, and any reoperation at follow-up. RESULTS: Of the 11 cases, 8 patients achieved successful wound healing by primary intention. Three patients showed partial necrosis in the edge of the skin graft, but the wound healed after standard wound care. Evaluation at 6 and 12 months after surgery showed that all patients had wound healing and mild local scarring; there was no obvious pigmentation or scar formation in the donor skin area. The average healing time was 37.5 days (range, 24-43 days). CONCLUSIONS: The HADM combined with split-thickness skin graft is a simple and effective reconstruction method for lacunar soft tissue defect of the lateral heel after calcaneal fracture. In this small sample, the combination demonstrated few infections, minor scar formation, few donor site complications, and relatively short hospital stays.

Optimal Treatment Parameters for Ultrasound-Stimulated Microbubbles in Upregulating Proliferation and Stemness of Bone Marrow Mesenchymal Stem Cells.

OBJECTIVES: Ultrasound-targeted microbubble disruption (UTMD) is a widely used technique to improve the differentiation and proliferation capacity of mesenchymal stem cells (MSCs), but the optimal therapeutic parameters for UTMD are unclear. In this study, we aimed to find the appropriate peak negative pressure (PNP), which is a key parameter for enhancing the stemness properties and proliferation of MSCs. METHODS: Experiments were performed in UTMD group, ultrasound (US) group under different PNP exposure conditions (0.5, 1.0, and 1.5 MPa), and control group. Apoptosis safety was analyzed by flow cytometry and MSC proliferation was measured at 12, 24, and 36 hours after irradiation by cell counting kit 8. The expression of the stemness genes NANOG, OCT-4, and SOX-2 were determined by enzyme-linked immunosorbent assay (ELISA) or reverse transcription polymerase chain reaction. RESULTS: The results showed that the 1.5 MPa UTMD-treated group had the highest proliferation capacity of MSCs at 24 hours. ELISA or quantitative reverse transcription polymerase chain reaction results showed that UTMD treatment of the 1.5 MPa group significantly upregulated the expression of the stemness genes NANOG, SOX-2, and OCT-4. CONCLUSIONS: In conclusion, the appropriate peak PNP value of UTMD was 1.5 MPa, and 1.5 MPa-mediated UTMD group obviously promoted MSCs proliferation and maintained stemness by upregulating the expression of stemness genes.

A survey of label-noise deep learning for medical image analysis.

Several factors are associated with the success of deep learning. One of the most important reasons is the availability of large-scale datasets with clean annotations. However, obtaining datasets with accurate labels in the medical imaging domain is challenging. The reliability and consistency of medical labeling are some of these issues, and low-quality annotations with label noise usually exist. Because noisy labels reduce the generalization performance of deep neural networks, learning with noisy labels is becoming an essential task in medical image analysis. Literature on this topic has expanded in terms of volume and scope. However, no recent surveys have collected and organized this knowledge, impeding the ability of researchers and practitioners to utilize it. In this work, we presented an up-to-date survey of label-noise learning for medical image domain. We reviewed extensive literature, illustrated some typical methods, and showed unified taxonomies in terms of methodological differences. Subsequently, we conducted the methodological comparison and demonstrated the corresponding advantages and disadvantages. Finally, we discussed new research directions based on the characteristics of medical images. Our survey aims to provide researchers and practitioners with a solid understanding of existing medical label-noise learning, such as the main algorithms developed over the past few years, which could help them investigate new methods to combat with the negative effects of label noise.

Homeobox B2 promotes malignant behavior and contributes to the radioresistance of nasopharyngeal carcinoma by regulating forkhead box protein O1.

Background: Nasopharyngeal carcinoma (NPC) is an epithelial tumor of the head and neck with heterogeneous racial and geographical distributions. Homeobox B2 (HOXB2) is a tumor promoter in many cancers. However, the biological role of HOXB2 in NPC has not been elucidated. Methods: Bioinformatics analysis was performed to identify the differentially expressed genes (DEGs) between samples of patients with radiosensitive and radioresistant NPC. qRT-PCR, western blotting and immunohistochemistry were used to detect the expression levels of the corresponding mRNA and proteins. Cell viability was detected by CCK-8 assay and colony-forming capability was evaluated using colony formation assays. Further, migration and invasion abilities were examined using wound-healing and transwell chamber assays, respectively. Cellular apoptosis after irradiation was assessed using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Results: HOXB2 was identified as a potential regulator of radioresistance in NPC. Our in vitro results indicate that HOXB2 overexpression (HOXB2-OE) promoted malignant behaviors including invasion, migration, proliferation, and inhibited the irradiation-induced apoptosis of NPC cells. Consistent with these results, HOXB2 knockdown (HOXB2-sh) exhibited the opposite trends in these biological activities. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs were enriched in the FOXO signaling pathway. Mechanistically, western blotting showed that HOXB2-OE inhibited forkhead box protein O1 (FOXO1) expression in NPC cells. Thereafter, we transferred the FOXO1-OE plasmid to HOXB2-OE NPC cells and found that overexpression of FOXO1 reversed cell proliferation, migration, invasion, and radioresistance profiles promoted by HOXB2 overexpression. Conclusion: Our findings showed that HOXB2 acts as a tumor promoter in NPC, activating malignant behaviors and radioresistance of tumors via FOXO1 regulation. Moreover, the inactivation of HOXB2 or activation of FOXO1 are potential strategies to inhibit tumor progression and overcome radioresistance in NPC.

Development and validation of a model and nomogram for breast cancer diagnosis based on quantitative analysis of serum disease-specific haptoglobin N-glycosylation.

BACKGROUND: A better diagnostic marker is in need to distinguish breast cancer from suspicious breast lesions. The abnormal glycosylation of haptoglobin has been documented to assist cancer diagnosis. This study aims to evaluate disease-specific haptoglobin (DSHp)-ß N-glycosylation as a potential biomarker for breast cancer diagnosis. METHODS: DSHp-ß chains of 497 patients with suspicious breast lesions who underwent breast surgery were separated from serum immunoinflammatory-related protein complexes. DSHp-ß N-glycosylation was quantified by mass spectrometric analysis. After missing data imputation and propensity score matching, patients were randomly assigned to the training set (n = 269) and validation set (n = 113). Logistic regression analysis was employed in model and nomogram construction. The diagnostic performance was analyzed with receiver operating characteristic and calibration curves. RESULTS: 95 N-glycopeptides at glycosylation sites N207/N211, N241, and N184 were identified in 235 patients with benign breast diseases and 262 patients with breast cancer. DSHp-ß N-tetrafucosyl and hexafucosyl were significantly increased in breast cancer compared with benign diseases (p < 0.001 and p = 0.001, respectively). The new diagnostic model and nomogram included GN2F2, G6N3F6, GN2FS at N184, G-N&G2S2, G2&G3NFS, G2N3F, GN3 at N207/N211, CEA, CA153, and could reliably distinguish breast cancer from benign diseases. For the training set, validation set, and training and validation sets, the area under the curves (AUCs) were 0.80 (95% CI: 0.75-0.86, specificity: 87%, sensitivity: 62%), 0.77 (95% CI:0.69-0.86, specificity: 75%, sensitivity: 69%), and 0.80 (95% CI:0.76-0.84, specificity: 77%, sensitivity: 68%), respectively. CEA, CA153, and their combination yielded AUCs of 0.62 (95% CI: 0.56-0.67, specificity: 29%, sensitivity: 90%), 0.65 (95% CI: 0.60-0.71, specificity: 74%, sensitivity: 51%), and 0.67 (95% CI: 0.62-0.73, specificity: 60%, sensitivity: 68%), respectively. CONCLUSIONS: The combination of DSHp-ß N-glycopeptides, CEA, and CA153 might be a better serologic marker to differentiate between breast cancer and benign breast diseases. The dysregulated N-glycosylation of serum DSHp-ß could provide insights into breast tumorigenesis.

An in vitro comparative study on clot lysis efficiency of urokinase and reteplase with the synergy of ultrasound needle.

Objectives: Ultrasound Needle, which is an improved ultrasonic horn device, has shown great potential for promoting the diffusion of thrombolytic drugs within clots and enhancing clot lysis efficiency. However, the clot lysis efficiency of different thrombolytic drugs with the synergy of Ultrasound Needle remains unknown. In this study, we aimed to compare the lysis efficiency of the non-fibrin-specific drug urokinase and fibrin-specific drug reteplase with the synergy of Ultrasound Needle. Materials and methods: Twenty-five milliliters of human blood was incubated for 1.5 h to form in vitro clots and then received the corresponding treatment protocols: control group (normal saline), US group (10 min of Ultrasound Needle treatment), UK group (30000IU of urokinase), r-PA group (2 mg of reteplase), US + UK group, and US + r-PA group. After treatment, the morphological changes of the clots were analyzed by B-mode ultrasound imaging and hematoxylin and eosin (H&E) staining. Lysis efficiency was evaluated based on the relative end weight (final weight/initial weight). The fibrin density of the different groups after treatment was assessed by immunofluorescence staining. Results: Morphological examination and relative end weight analysis showed that combination therapies induced a more thorough dissolution of clots compared with single therapies, and the US + r-PA group exhibited higher lysis efficiency than the US + UK group. In addition, immunofluorescence staining showed that the US + r-PA group had fewer remaining thrombus fibrins than the US + UK group after treatment. Conclusions: The Ultrasound Needle can significantly improve the clot lysis efficiency of both fibrinolytic drugs, and fibrin-specific reteplase exhibited superior lysis efficiency over non-fibrin-specific urokinase with the synergy of the Ultrasound Needle.

Corn Oligopeptide Alleviates Nonalcoholic Fatty Liver Disease by Regulating the Sirtuin Signaling Pathway.

Nonalcoholic fatty liver disease (NAFLD) represents the most prevalent type of chronic liver disease, spanning from simple steatosis to nonalcoholic steatohepatitis (NASH). Corn oligopeptide (CP) is a functional peptide known for its diverse pharmacological effects on metabolism. In this study, we evaluated the protective activity of CP against fatty liver disease. Oral administration of CP significantly reduced body weight gain by 2.95%, serum cholesterol by 22.54%, and liver injury, as evidenced by a reduction of 32.19% in serum aspartate aminotransferase (AST) and 49.10% in alanine aminotransferase (ALT) levels in mice subjected to a high-fat diet (HFD). In a streptozotocin/HFD-induced NASH mouse model, CP attenuated body weight gain by 5.11%, liver injury (with a 34.15% decrease in AST and 11.43% decrease in ALT), and, to some extent, liver inflammation and fibrosis. Proteomic analysis revealed the modulation of oxidative phosphorylation and sirtuin (SIRT) signaling pathways by CP. Remarkably, CP selectively inhibited the hepatic expression of mitochondrial SIRT3 and SIRT5 in both HFD and NASH models. In summary, CP demonstrates a preventive effect against metabolic-stress-induced NAFLD progression by modulating oxidative stress and the SIRT signaling pathway, suggesting the potential of CP as a therapeutic agent for the treatment of NAFLD and advanced-stage NASH.

Serum MYCN as a predictive biomarker of prognosis and therapeutic response in the prevention of hepatocellular carcinoma recurrence.

The proto-oncogene MYCN expression marked a cancer stem-like cell population in hepatocellular carcinoma (HCC) and served as a therapeutic target of acyclic retinoid (ACR), an orally administered vitamin A derivative that has demonstrated promising efficacy and safety in reducing HCC recurrence. This study investigated the role of MYCN as a predictive biomarker for therapeutic response to ACR and prognosis of HCC. MYCN gene expression in HCC was analyzed in the Cancer Genome Atlas and a Taiwanese cohort (N = 118). Serum MYCN protein levels were assessed in healthy controls (N = 15), patients with HCC (N = 116), pre- and post-surgical patients with HCC (N = 20), and a subset of patients from a phase 3 clinical trial of ACR (N = 68, NCT01640808). The results showed increased MYCN gene expression in HCC tumors, which positively correlated with HCC recurrence in non-cirrhotic or single-tumor patients. Serum MYCN protein levels were higher in patients with HCC, decreased after surgical resection of HCC, and were associated with liver functional reserve and fibrosis markers, as well as long-term HCC prognosis (>4 years). Subgroup analysis of a phase 3 clinical trial of ACR identified serum MYCN as the risk factor most strongly associated with HCC recurrence. Patients with HCC with higher serum MYCN levels after a 4-week treatment of ACR exhibited a significantly higher risk of recurrence (hazard ratio 3.27; p = .022). In conclusion, serum MYCN holds promise for biomarker-based precision medicine for the prevention of HCC, long-term prognosis of early-stage HCC, and identification of high-response subgroups for ACR-based treatment.

Assembly of CpcL-phycobilisomes.

CpcL-phycobilisomes (CpcL-PBSs) are a reduced type of phycobilisome (PBS) found in several cyanobacteria. They lack the traditional PBS terminal energy emitters, but still show the characteristic red-shifted fluorescence at ~670 nm. We established a method of assembling in vitro a rod-membrane linker protein, CpcL, with phycocyanin, generating complexes with the red-shifted spectral features of CpcL-PBSs. The red-shift arises from the interaction of a conserved key glutamine, Q57 of CpcL in Synechocystis sp. PCC 6803, with a single phycocyanobilin chromophore of trimeric phycocyanin at one of the three ß82-sites. This chromophore is the terminal energy acceptor of CpcL-PBSs and donor to the photosystem(s). This mechanism also operates in PBSs from Acaryochloris marina MBIC11017. We then generated multichromic complexes harvesting light over nearly the complete visible range via the replacement of phycocyanobilin chromophores at sites α84 and ß153 of phycocyanins by phycoerythrobilin and/or phycourobilin. The results demonstrate the rational design of biliprotein-based light-harvesting elements by engineering CpcL and phycocyanins, which broadens the light-harvesting range and accordingly improves the light-harvesting capacity and may be potentially applied in solar energy harvesting.

Survival benefit of adjuvant chemotherapy after resection of Stage I lung adenocarcinoma containing micropapillary components.

BACKGROUND: The usefulness of postoperative adjuvant chemotherapy (ACT) for patients with stage I lung adenocarcinoma with micropapillary (MIP) components remains unclear. We analyzed whether postoperative ACT could reduce recurrence in patients with stage I lung adenocarcinoma with MIP components, thereby improving their overall survival (OS) and disease-free survival (DFS). METHODS: Data for patients with pathologically confirmed stage I lung adenocarcinoma with MIP components from January 2012 to December 2018 were retrospectively analyzed. OS and DFS were analyzed in groups and subgroups. RESULTS: Overall, 259 patients were enrolled. Patients who received ACT in stage IA showed significantly better survival than did those with no-adjuvant chemotherapy (NACT); (5-year OS 89.4% vs. 73.6%, p < 0.001; 5-year DFS 87.2% vs. 66.0%, p = 0.008). A difference was also observed for in-stage IB patients (5-year OS 82.0% vs. 51.8%, p = 0.001; 5-year DFS 76.0% vs. 41.11 %, p = 0.004). In subgroup analysis based on the proportion of MIP components, patients with 1%-5% MIP components had a significantly better prognosis in the ACT group than in the NACT group (5-year OS 82.4% vs. 66.0%, p = 0.005; 5-year DFS 76.5% vs. 49.1%, p = 0.032). A similar difference was observed for patients with MIP ≥5% (5-year OS 80.7% vs. 47.8%, p = 0.009; 5-year DFS 73.11% vs. 43.5%, p = 0.007). CONCLUSION: Among patients with stage I lung adenocarcinoma with MIP components, those who received ACT showed significant survival benefits compared to those without ACT. Patients with lung adenocarcinoma with MIP components could benefit from ACT when the MIP was ≥1%.

Multivitamin consumption and childhood asthma: a cross-sectional study of the NHANES database.

BACKGROUND: Dietary intakes of vitamins are associated with asthma. However, previous studies mainly explored the association between a single vitamin intake and asthma, which did not take the multivitamins into consideration. Herein, this study aims to explore the overall effect of dietary multivitamins consumption on childhood asthma. METHODS: Data of children and adolescents (aged 2-17 years old) were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2015-2018 in this cross-sectional study. Weighted univariate logistic regression analysis was used to screen covariates. The association between multivitamins (including vitamin A, C, D, E, B1, B2, B6, B12, K, niacin, folic acid, and choline) and childhood asthma was explored using univariate and multivariate logistic regression analyses. The evaluation indexes were odds ratio (OR) and 95% confidence interval (CI). We further introduced the Bayesian kernel machine regression (BKMR) to assess the joint effect of the twelve vitamins on childhood asthma, the impact of an individual vitamin as part of a vitamin mixture, and the potential interactions among different vitamins. RESULTS: Among 4,715 eligible children and adolescents, 487 (10.3%) had asthma. After adjusting for covariates including race, family history of asthma, pregnant smoking, BMI Z-score, energy intake, breast feeding, and low birth weight, we found that for each 1-unit increase in vitamin K consumption, the odds of childhood asthma decreased 0.99 (P=0.028). The overall effect analysis reported a trend of negative relationship between the multivitamins and childhood asthma, especially at the 75th percentile and over. According to the BKMR models, when other vitamins are fixed at the median level, the odds of childhood asthma increased along with the elevated vitamin D (VD) and vitamin B2 (VB2), whereas along with the depressed vitamin C (VC). In addition, no potential interaction has been found between every two vitamins of multivitamins on childhood asthma. CONCLUSION: Among children and adolescents who have high-risk of asthma, it may be beneficial to increase dietary consumption of multivitamins. Our findings recommended that children and adolescents should increase the intake of VC-rich foods, whereas control the dietary consumption of VD and VB2 in daily life.