Observations of the effectiveness, dosage, and prognosis of intensity-modulated radiation therapy under ultrasonic guidance for cervical cancer patients.

BACKGROUND: Volumetric modulated arc therapy (VMAT) guided by ultrasound is a novel radiation therapy technique that facilitates the delineation of the tumor target area under image guidance, enhancing the precision of radiation therapy and maximizing the protection of surrounding tissues. OBJECTIVE: The objective of this paper is to investigate the effectiveness of VMAT under ultrasonic guidance for cervical cancer patients and its impact on radiotherapy dosage and prognosis. METHODS: A retrospective analysis encompassed 128 instances of cervical cancer patients who were admitted to our medical facility between April 2019 and April 2021. The patients were categorized into an observation cohort and a control cohort, depending on variations in treatment modalities post-admission. The control group underwent conventional radiotherapy, whereas the observation group received VMAT guided by ultrasound. Clinical efficacy, average radiation dosages (in the radiotherapy target area, rectum, and bladder), radiotherapy-related toxicities during treatment, and one-year survival rates were compared between the two groups. Additionally, variances in pre- and post-treatment serum levels of squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate antigen 724 (CA724) were subjected to assessment. RESULTS: When compared to the control group (64.52%), the observation cohort's comprehensive effectiveness rate was considerably greater (80.30%). The observation group saw lower average radiation exposures and a reduction in the post-treatment concentrations of CEA, SCC-Ag, and CA724. The overall incidence of adverse effects from radiation treatment also declined. The observation group had a greater one-year survival rate (90.48%) than the control group (73.33%). When comparing the observation cohort to the control group, Kaplan-Meier survival analysis showed a significantly higher one-year survival rate (Log-Rank = 6.530, P= 0.011). CONCLUSION: VMAT guided by ultrasound for patients with cervical cancer demonstrates promising short- and long-term treatment outcomes. It also leads to improvements in serum CEA, SCC-Ag, and CA724 levels, as well as reductions in the average radiation dosages to the radiotherapy target area, rectum, and bladder. This approach warrants attention from clinicians in clinical practice.

Aberrant SUMO2/3 modification of RUNX1 upon SENP1 inhibition is linked to the development of diabetic retinopathy in mice.

Our previous report established that RUNX family transcription factor 1 (RUNX1) promotes proliferation of mouse retinal microvascular endothelial cells (mRMECs) and exacerbates diabetic retinopathy (DR). However, the mechanism behind the upregulation of RUNX1 remains unclear. This study aims to investigate the possible correlation between histone SUMOylation and RUNX1 in DR, as well as the involved molecules. A mouse model of diabetes was induced by streptozotocin (STZ). These mice had increased retinal thickness and elevated production of inflammatory cytokines. Additionally, they showed elevated levels of SUMO1 and SUMO2/3, but reduced levels of SUMO specific peptidase 1 (SENP1) in retinal tissues. Co-immunoprecipitation and Western blot assays revealed that the RUNX1 protein was primarily modified by SUMO2/3, and SENP1 inhibited SUMO2/3 modification, thereby reducing RUNX1 expression. Overexpression of SENP1 alleviated symptoms in mice and alleviated inflammation. In vitro experiments demonstrated that the SENP1 overexpression suppressed the proliferation, migration, and angiogenesis of high-glucose-induced mRMECs. However, further overexpression of RUNX1 counteracted the alleviating effects of SENP1 both in vivo and in vitro. In conclusion, this study demonstrates that the downregulation of SENP1 in DR leads to SUMO2/3-dependent activation of RUNX1. This activation promotes proliferation of mRMECs and exacerbates DR symptoms in mice.

Evaluating the Accuracy of Breast Cancer and Molecular Subtype Diagnosis by Ultrasound Image Deep Learning Model.

Background: Breast ultrasound is the first choice for breast tumor diagnosis in China, but the Breast Imaging Reporting and Data System (BI-RADS) categorization routinely used in the clinic often leads to unnecessary biopsy. Radiologists have no ability to predict molecular subtypes with important pathological information that can guide clinical treatment. Materials and Methods: This retrospective study collected breast ultrasound images from two hospitals and formed training, test and external test sets after strict selection, which included 2,822, 707, and 210 ultrasound images, respectively. An optimized deep learning model (DLM) was constructed with the training set, and the performance was verified in both the test set and the external test set. Diagnostic results were compared with the BI-RADS categorization determined by radiologists. We divided breast cancer into different molecular subtypes according to hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression. The ability to predict molecular subtypes using the DLM was confirmed in the test set. Results: In the test set, with pathological results as the gold standard, the accuracy, sensitivity and specificity were 85.6, 98.7, and 63.1%, respectively, according to the BI-RADS categorization. The same set achieved an accuracy, sensitivity, and specificity of 89.7, 91.3, and 86.9%, respectively, when using the DLM. For the test set, the area under the curve (AUC) was 0.96. For the external test set, the AUC was 0.90. The diagnostic accuracy was 92.86% with the DLM in BI-RADS 4a patients. Approximately 70.76% of the cases were judged as benign tumors. Unnecessary biopsy was theoretically reduced by 67.86%. However, the false negative rate was 10.4%. A good prediction effect was shown for the molecular subtypes of breast cancer with the DLM. The AUC were 0.864, 0.811, and 0.837 for the triple-negative subtype, HER2 (+) subtype and HR (+) subtype predictions, respectively. Conclusion: This study showed that the DLM was highly accurate in recognizing breast tumors from ultrasound images. Thus, the DLM can greatly reduce the incidence of unnecessary biopsy, especially for patients with BI-RADS 4a. In addition, the predictive ability of this model for molecular subtypes was satisfactory,which has specific clinical application value.

Pneumocystis jiroveci pneumonia, Nocardia brasiliensis, and Mycobacterium tuberculosis co-infection in a myasthenia gravis patient: A case report.

RATIONALE: Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junctions that leads to fluctuating weakness and disabling fatigability. Due to difficulty in breathing caused by weakness of the respiratory muscles, patients with MG are more susceptible to pneumonia and other respiratory infections. As many patients with MG are given immunosuppressive therapy, this makes them more prone to infections. However, coinfection with 3 pathogens is very rare. PATIENT CONCERNS: Here, we report the case of a 41-year-old gentleman with MG who was receiving long-term steroid therapy. He presented with a cough with pale brown expectoration that occurred without obvious inducement, severe pain in the scapula, as well as swelling and weakness of both legs. Despite undergoing treatment, but his symptoms did not improve, prompting two additional hospital admissions over a period of several months. DIAGNOSIS: Bronchoscopy and bronchoalveolar lavage (BAL) were performed, revealing the presence of Pneumocystis jirovecii , Nocardia brasiliensis, and Mycobacterium tuberculosis (MTB). N brasiliensis was identified by positive modified acid-fast Kinyoun staining as well as a positive colony culture identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry from the BAL sample. MTB was confirmed using GeneXpert, and due to the limitations of the culture conditions, methenamine silver stain was used to confirm Pneumocystis jirovecii. Next-generation sequencing (NGS) assay of the BAL samples also confirmed these pathogens. INTERVENTIONS: The patient was transferred to a designated tuberculosis hospital and received anti-infective and anti-TB treatment. OUTCOMES: During treatment at the designated hospital, the patient developed gastrointestinal bleeding and impaired liver function. One month later, he developed multiple organ failure, consolidation of the left lower lung, and pan-drug resistant bacteremia. He refused further treatment and was discharged. CONCLUSION: In conclusion, physicians should be aware of the predisposition of MG patients to co-infections, especially patients with metabolic disorders, to avoid inadequate treatment and poor patient outcomes. Due to the limitations of culture conditions, NGS should be considered as a new technique for identifying pathogens.

New Aspects of Ultrasound-Mediated Targeted Delivery and Therapy for Cancer.

Ultrasound-mediated targeted delivery (UMTD), a novel delivery modality of therapeutic materials based on ultrasound, shows great potential in biomedical applications. By coupling ultrasound contrast agents with therapeutic materials, UMTD combines the advantages of ultrasound imaging and carrier, which benefit deep tissue penetration and high concentration aggregation. In this paper we introduced recent advances in ultrasound contrast agents and applications in tumor therapy. Ultrasound contrast agents were categorized by their functions, mainly including thermosensitive, pH-sensitive and photosensitive ultrasound contrast agents. The various applications of UMTD in tumor treatment were summarized as follows: drug therapy, transfection of anti-oncogene, RNA interference, vaccine immunotherapy, monoclonal antibody immunotherapy, adoptive cellular immunotherapy, cytokine immunotherapy, and so on. In the end, we elaborated on the current challenges and provided perspectives of UMTD for clinical applications.

2-Hydroxy-oleic acid does not activate sphingomyelin synthase activity.

2-Hydroxy-oleic acid (2OHOA) is a potent anticancer drug that induces cancer cell cycle arrest and apoptosis. Previous studies have suggested that 2OHOA's anticancer effect is mediated by SMS activation in cancer cells, including A549 and U118 cells. To confirm this phenomenon, in this study, we treated both A549 and U118 cells with 2OHOA and measured SMS activity. To our surprise, we found neither 2OHOA-mediated SMS activation nor sphingomyelin accumulation in the cells. However, we noted that 2OHOA significantly reduces phosphatidylcholine in these cells. We also did not observe 2OHOA-mediated SMS activation in mouse tissue homogenates. Importantly, 2OHOA inhibited rather than activated recombinant SMS1 (rSMS1) and rSMS2 in a dose-dependent fashion. Intra-gastric treatment of C57BL/6J mice with 2OHOA for 10 days had no effects on liver and small intestine SMS activities and plasma sphingomyelin levels. The treatment inhibited lysophosphatidylcholine acyltransferase (LPCAT) activity, consistent with the aforementioned reduction in plasma phosphatidylcholine. Because total cellular phosphatidylcholine is used as a predictive biomarker for monitoring tumor responses, the previously reported 2OHOA-mediated cancer suppression could be related to this phosphatidylcholine reduction, which may influence cell membrane structure and properties. We conclude that 2OHOA is not a SMS activator and that its anticancer property may be related to an effect on phosphatidylcholine metabolism.

Complete genome sequence of human pathogen Kosakonia cowanii type strain 888-76T

ABSTRACT Kosakonia cowanii type strain 888-76T is a human pathogen which was originally isolated from blood as NIH group 42. In this study, we report the complete genome sequence of K. cowanii 888-76T. 888-76T has 1 chromosome and 2 plasmids with a total genome size of 4,857,567 bp and C+G 56.15%. This genome sequence will not only help us to understand the virulence features of K. cowanii 888-76T but also provide us the useful information for the study of evolution of Kosakonia genus.

Triphenyl Phosphine-Functionalized Chitosan Nanoparticles Enhanced Antitumor Efficiency Through Targeted Delivery of Doxorubicin to Mitochondria.

Mitochondria as an important organ in eukaryotic cells produced energy through oxidative phosphorylation and also played an important role in regulating the apoptotic signal transduction process. Importantly, mitochondria like nuclei also contained the functional DNA and were very sensitive to anticancer drugs which could effectively inhibit the synthesis of nucleic acid, especially the production of DNA. In this work, we designed novel triphenyl phosphine (TPP)-conjugated chitosan (CS) nanoparticles (NPs) for efficient drug delivery to cell mitochondria. The results showed that compared with free doxorubicin (Dox), Dox-loaded TPP-NPs were specifically distributed in mitochondria of tumor cells and interfered with the function of mitochondria, thus resulted in the higher cytotoxicity and induced the significant cell apoptosis effect. Taken together, triphenyl phosphine-conjugated chitosan nanoparticles may become a promising mitochondria-targeting nanocarrier candidate for enhancing antitumor effects.

Hyaluronic acid-coated chitosan nanoparticles induce ROS-mediated tumor cell apoptosis and enhance antitumor efficiency by targeted drug delivery via CD44.

BACKGROUND: A targeted drug nanoparticle (NP) delivery system has shown potential as a possible cancer treatment. Given its merits, such as its selective distribution at tumor sites and its controllable drug release, drug-loaded NPs can be effectively delivered to selected organs and targeted cells, thus enhancing its antitumor efficiency and reducing its toxicity. METHODS: We reported that hyaluronic acid (HA)-coated chitosan NPs promoted the drug delivery of 5-fluorouracil (5-Fu) into tumor cells that highly expressed CD44. RESULTS: Our new findings suggested that HA-coated chitosan NPs enhanced drug accumulation by effectively transporting NPs into CD44-overexpressed tumor cells, and they also resulted in mitochondrial damage induced by the production of reactive oxygen species (ROS). Compared to free drug and uncoated NPs, HA-coated chitosan NPs exhibited stronger inhibition rates and induced obvious apoptosis in CD44-overexpressed A549 cells. CONCLUSIONS: Biocompatible and biodegradable HA-coated chitosan NPs were developed to encapsulate a chemotherapeutic drug (5-Fu) to enhance drug accumulation in tumor cells and to improve the agent's antitumor efficiency by offering targeted drug delivery via CD44.

Preparation and characterization of novel chitosan-protamine nanoparticles for nucleus-targeted anticancer drug delivery.

It is well known that most anticancer drugs commonly show high toxicity to the DNA of tumor cells and exert effects by combining with the DNA or associated enzymes in the nucleus. Most developed drugs are first delivered into the cytoplasm and then transferred to the nucleus through the membrane pores. Sometimes, the transportation of drugs from cytoplasm to nucleus is not efficient and often results in poor therapeutic effects. In this study, we developed special and novel nanoparticles (NPs) made of chitosan and protamine for targeted nuclear capture of drugs to enhance anticancer effects. The anticancer effects of nuclear targeted-delivery of drugs in NPs were also evaluated by investigating cytotoxicity, cellular uptake mechanism, and cell apoptosis on cells. Chitosan-protamine NPs were characterized by good drug entrapment, sustained release, small average particle size, low polydispersity index, and high encapsulation efficiency; and accomplished the efficient nuclear delivery of fluorouracil (5-Fu). Compared with free 5-Fu and 5-Fu-loaded chitosan NPs, treatment of A549 cells and HeLa cells with 5-Fu-loaded chitosan-protamine NPs showed the highest cytotoxicity and further induced the significant apoptosis of cells. In addition, 5-Fu-loaded chitosan-protamine NPs exhibited the best efficiency in inhibiting tumor growth than the other three formulations. 5-Fu-loaded chitosan-protamine NPs enhanced antitumor efficacy through the targeted nuclear capture of drugs and showed promising potential as a nanodelivery system for quickly locating drugs in the nucleus of cells.