Signal mining and gender differences analysis of adverse events in NMIBC treatment with gemcitabine and BCG bladder instillation based on the FAERS database.

OBJECTIVE: To explore safety differences and perform a gender-based analysis of adverse events related to gemcitabine and Bacillus Calmette-Guérin (BCG) vaccine using the U.S. FDA Adverse Event Reporting System (FAERS) database. METHODS: Using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods, adverse events associated with gemcitabine and BCG were mined from FAERS database reports spanning from Q1 2004 to Q3 2023. RESULTS: The study extracted 37,855 reports with gemcitabine and 5,455 reports with BCG as the primary suspected drugs. Adverse events were more prevalent in males (male-to-female ratio: gemcitabine 1.10, BCG 4.25). Differences in high-frequency adverse events among the top 20 signals were detected for both drugs. Both drugs affected similar organ systems, including potential pulmonary, ocular, and renal toxicity, with gemcitabine showing a broader range of adverse events. Gender analysis revealed fewer adverse reactions to gemcitabine in females, while males had fewer adverse reactions to BCG. CONCLUSION: Differences in high-frequency adverse events between gemcitabine and BCG, including some not listed on drug labels, were observed. Both drugs affect similar organ systems, with gemcitabine showing a broader range of adverse events. Gender differences in adverse events were notable.

Right Sinus of Valsalva Aneurysm and Dissection into the Interventricular Septum: A Case Report.

Sinus of Valsalva aneurysm (SVA) is considered to be an uncommon cardiac anomaly, carrying a very high rate of mortality. After treatment, the prognosis is excellent. Thus, it is important to make a timely diagnosis and clarify the anatomical details of the SVA. Here, we report a right SVA with dissection into the interventricular septum, with bulging and incomplete rupture into the left outflow tract. The SVA was evaluated using echocardiography (transoesophageal, transthoracic, and three-dimensional echocardiography) and cardiac computed tomography (CT), especially three-dimensional reconstruction, to help us plan the surgical approach. After surgery, the patient's recovery was favorable.

Bifidobacterium bifidum-Mediated Specific Delivery of Nanoparticles for Tumor Therapy.

PURPOSE: Hypoxia is considered to be obstructive to tumor treatment, but the reduced oxygen surroundings provide a suitable habitat for Bifidobacterium bifidum (BF) to colonize. The anaerobe BF selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. Therefore, BF may be a potential targeting agent which could be used effectively in tumor treatment. We aimed to determine whether a novel BF-mediated strategy, that was designed to deliver AP-PFH/PLGA NPs (aptamers CCFM641-5-functionalized Perfluorohexane (PFH) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles) by aptamer-directed approach into solid tumor based on the tumor-targeting ability of BF, could improve efficiency of high intensity focused ultrasound (HIFU) treatment of breast cancer. METHODS: We synthesized AP-PFH/PLGA NPs using double emulsion method and carbodiimide method. Then, we evaluated targeting ability of AP-PFH/PLGA NPs to BF in vivo. Finally, we studied the efficacy of HIFU ablation based on BF plus AP-PFH/PLGA NPs (BF-mediated HIFU ablation) in tumor. RESULTS: The elaborately designed AP-PFH/PLGA NPs can target BF colonized in tumor to achieve high tumor accumulation, which can significantly enhance HIFU therapeutic efficiency. We also found that, compared with traditional chemotherapy, this therapy not only inhibits tumor growth, but also significantly prolongs the survival time of mice. More importantly, this treatment strategy has no obvious side effects. CONCLUSION: We successfully established a novel therapy method, BF-mediated HIFU ablation, which provides an excellent platform for highly efficient and non-invasive therapy of tumor.

Intravenous misplacement of the nephrostomy catheter following percutaneous nephrostolithotomy: a case report and literature review.

Intravenous misplacement of the nephrostomy catheter following percutaneous nephrostolithotomy (PCNL) is extremely rare, and little information is available about this complication. Because the patient's prognosis may be poor, sufficient attention should be paid to early identification and treatment of this complication. We present an uncommon case of a patient with intravenous nephrostomy catheter misplacement after PCNL at our hospital. In our patient, the tip of the nephrostomy catheter was located in the inferior vena cava. It was successfully managed using two-step catheter withdrawal under fluoroscopy, and the percutaneous nephrostomy catheter was able to be withdrawn 7 to 8 cm back into the collecting system in stages with the surgical team on standby. There were no severe complications such as deep vein thrombosis that developed during or after the catheter withdrawal. Patients could be managed conservatively using intravenous antibiotics, strict bed rest, and tube withdrawal using computed tomography (CT) or fluoroscopy guide in most cases combined with information in the literature. Additionally, open surgery could be used as an alternative treatment.

Multifunctional Nanoparticles Encapsulating Astragalus Polysaccharide and Gold Nanorods in Combination with Focused Ultrasound for the Treatment of Breast Cancer.

PURPOSE: Focused ultrasound (FUS) is a noninvasive method to produce thermal and mechanical destruction along with an immune-stimulatory effect against cancer. However, FUS ablation alone appears insufficient to generate consistent antitumor immunity. In this study, a multifunctional nanoparticle was designed to boost FUS-induced immune effects and achieve systemic, long-lasting antitumor immunity, along with imaging and thermal enhancement. MATERIALS AND METHODS: PEGylated PLGA nanoparticles encapsulating astragalus polysaccharides (APS) and gold nanorods (AuNRs) were constructed by a simple double emulsion method, characterized, and tested for cytotoxicity. The abilities of PA imaging and thermal-synergetic ablation efficiency were analyzed in vitro and in vivo. The immune-synergistic effect on dendritic cell (DC) differentiation in vitro and the immune response in vivo were also evaluated. RESULTS: The obtained APS/AuNR/PLGA-PEG nanoparticles have an average diameter of 255.00±0.1717 nm and an APS-loading efficiency of 54.89±2.07%, demonstrating their PA imaging capability and high biocompatibility both in vitro and in vivo. In addition, the as-prepared nanoparticles achieved a higher necrosis cell rate and induced apoptosis rate in an in vitro cell suspension assay, greater necrosis area and decreased energy efficiency factor (EEF) in an in vivo rabbit liver assay, and remarkable thermal-synergic performance. In particular, the nanoparticles upregulated the expression of MHC-II, CD80 and CD86 on cocultured DCs in vitro, followed by declining phagocytic function and enhanced interleukin (IL)-12 and interferon (INF)-γ production. Furthermore, they boosted the production of tumor necrosis factor (TNF)-α, IFN-γ, IL-4, IL-10, and IgG1 (P< 0.001) but not IgG2a. Immune promotion peaked on day 3 after FUS in vivo. CONCLUSION: The multifunctional APS/AuNR/PLGA-PEG nanoparticles can serve as an excellent synergistic agent for FUS therapy, facilitating real-time imaging, promoting thermal ablation effects, and boosting FUS-induced immune effects, which have the potential to be used for further clinical FUS treatment.

Feasibility between Bifidobacteria Targeting and Changes in the Acoustic Environment of tumor Tissue for Synergistic HIFU.

High intensity focused ultrasound (HIFU) has been recently shown as a rapidly developing new technique for non-invasive ablation of local tumors whose therapeutic efficiency can be significantly improved by changing the tissue acoustic environment (AET). Currently, the method of changing AET is mainly to introduce a medium with high acoustic impedance, but there are some disadvantages such as low retention of the introduced medium in the target area and a short residence time during the process. In our strategy, anaerobic bacterium Bifidobacterium longum (B. longum) which can colonize selectively in hypoxic regions of the animal body was successfully localized and shown to proliferate in the hypoxic zone of tumor tissue, overcoming the above disadvantages. This study aimed to explore the effects of Bifidobacteria on AET (including the structure and acoustic properties of tumor tissues) and HIFU ablation at different time. The results show that the injection of Bifidobacteria increased the collagen fibre number, elastic modulus and sound velocity and decreased neovascularization in tumor tissues. The number of collagen fibres and neovascularization decreased significantly over time. Under the same HIFU irradiation intensity, the B. longum injection increased the coagulative necrosis volume and decreased the energy efficiency factor (EEF). This study confirmed that Bifidobacteria can change the AET and increase the deposition of ultrasonic energy and thereby the efficiency of HIFU. In addition, the time that Bifidobacteria stay in the tumor area after injection is an important factor. This research provides a novel approach for synergistic biologically targeted HIFU therapy.

[Effect of Bifidobacterium-induced changes in tumor tissue acoustic properties on efficacy of high-intensity focused ultrasound ablation].

OBJECTIVE: To investigate the effects of Bifidobacterium on the acoustic characteristics of tumor tissue and how such acoustic changes affect the efficacy of high-intensity focused ultrasound (HIFU) ablation in nude mice. METHODS: Forty mice bearing human breast cancer cell (MDA-MB-231) xenograft were randomized into experimental group (n=20) and control group (n=20) for intravenous injection of Bifidobacterium suspension (200 µL, 4 × 108 cfu/mL) and PBS (200 µL) for 3 consecutive days, respectively. Before and at 3 and 7 days after the first injection, shear wave elastography was used to evaluate the hardness of the tumor tissue. On day 7 after the first injection, 10 mice from each group were sacrificed and the sound velocity and sound attenuation of the tumor tissues were measured. The changes in the collagen fibers in the tumors were evaluated using Masson staining, and neovascularization in the tumor was assessed with immunohistochemistry for platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31). The remaining 10 tumor-bearing mice in each group were subjected to HIFU ablation, and the ablation efficiency was evaluated by assessing the changes in irradiation gray values, coagulative necrosis volume, energy efficiency factor (EEF) and irradiation area and by pathological examination with HE staining. RESULTS: In the experimental group, the collagen fibers in the tumor tissues were strong and densely aligned, and the tumors contained fewer new blood vessels showing strip-or spot-like morphologies. In the control group, the collagen fibers in the tumors were thin and loosely arranged, and the tumors showed abundant elongated or round new blood vessels. Bifidobacterium colonized in the tumor 7 days after the injection, and the tumor hardness was significantly greater in the experimental group than in the control group (P=0.01); the acoustic velocity (P=0.001) and the acoustic attenuation (P=0.000) of the tumor tissues were also greater in the experimental group. HIFU irradiation resulted in significantly greater changes in the gray scale of tumor (P=0.0006) and larger coagulative necrosis volume (P=0.0045) in the experimental group than in the control group, and the EEF was significantly smaller in the experimental group (P=0.0134). CONCLUSIONS: Bifidobacterium can cause changes in collagen fiber content, acoustic velocity and attenuation in the tumor tissue and reduce the EEF of HIFU irradiation, thereby improving the efficacy of HIFU irradiation.

Nanoparticles conjugated with bacteria targeting tumors for precision imaging and therapy.

The hypoxic region microenvironment reduces the susceptibility of the cancer cells to radiotherapy and anticancer drugs of the solid tumors. However, the reduced oxygen surroundings provide an appreciable habitat for anaerobic bacteria to colonize and proliferate. Herein, we present a biocompatible bacteriabased system that can deliver poly(lactic-co-glycolic acid)(PLGA) nanoparticles(PLGA NPs) specifically targeting into solid tumor to achieve precision imaging and treatment. In our strategy, anaerobic bacterium Bifidobacterium longum (B. longum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to conjugate with PLGA NPs and transported into solid tumors. To improve the efficacy and specificity of tumor therapy, low-boiling point perfluorohexane (PFH) liquid was wrapped in the core of PLGA NPs (PFH/PLGA NPs), which could increase the deposition of energy by affecting the acoustic environment of the tumor and destroy cells after liquid-gas phase transition during High Intensity Focused Ultrasound (HIFU) irradiation. This strategy shows an effective diagnosis and treatment integration for giving stronger imaging, longer retention period and more effective tumor therapy.

Experimental Study of Retention on the Combination of Bifidobacterium with High-Intensity Focused Ultrasound (HIFU) Synergistic Substance in Tumor Tissues.

High intensity focused ultrasound (HIFU) has been recently regarded to be a new type of technique for non-invasive ablation of local tumors and HIFU synergists could significantly improve its therapeutic efficiency. The therapeutic efficiency of HIFU is greatly limited by the low retention of HIFU synergists in the target area and short residence time. This study aimed to explore a method to increase the deposition of HIFU synergists in tumors. Cationic lipid nanoparticle can be used to enhance the HIFU ablation effect, but there is still a problem for it that the deposition amount in the tumor tissue is small and the residence time is short. Bifidobacterium is highly biosafe and can be selectively colonized in the hypoxic zone of tumor tissue. Cationic lipid nanoparticles can be observed in vitro by attachment to bifidobacterium by electrostatic adsorption. And the effect of the proliferation of bifidobacterium in tumor tissues on the retention amount and retention time of cationic lipid nanoparticles in vivo was evaluated. Results showed that the cationic lipid nanoparticles were linked to the surface of Bifidobacterium effectively in vitro, while in vivo, the retention amount and retention time of cationic lipid nanoparticles could be increased by Bifidobacterium in tumor tissues, which provided a new method for improving the therapeutic efficiency of HIFU.

[Establishment of an animal model of blunt scrotal trauma and evaluation of the lesion by conventional and contrast-enhanced ultrasonography].

OBJECTIVE: To establish an animal model of acute blunt scrotal trauma (BST) and evaluate the types of lesion by conventional ultrasonography (CUS) and contrast-enhanced ultrasonography (CEUS). METHODS: We made acute BST models in 21 healthy male New Zealand rabbits by striking 3 - 12 times the unilateral testes randomly selected with a 0. 5 kg iron ball falling freely from a 30 cm height. Then we evaluated the lesion types in the models by CUS and CEUS and verified our evaluation against pathological results. RESULTS: Acute BST models were successfully established in all the 21 animals, including contusion in 10, hematoma in 6, and rupture in 5, all confirmed by pathology. CUS clearly manifested the morphology, internal echoes, and blood flow of the testes, but had a low rate of accurate diagnosis in testicular contusion for over 6 hours as well as in complex lesions. CEUS revealed an earlier perfusion of the contrast agent and shorter arriving time (AT) and time to peak intensity ( TP) in testicular contusion than in the control testes (P <0.05) , but showed no statistically significant difference between the two groups in the half time of descending peak intensity (P>0.05). For testicular hematoma, contrast agent clearly presented its outline and a delayed low enhancement in the surrounding tissue, with significant differences from the control in AT and TTP. In severe testis rupture, occasional outflow but no perfusion of contrast agent was observed. CONCLUSION: BST models can be established in rabbits by repeated strikes of the unilateral testes lesion of contrast agent was observed. with a freely falling iron ball. Simple contusion injury can be induced by less than 6 strikes, while complex injuries can be inflicted by more than 10. Combined application of CUS and CEUS can improve the accuracy of diagnosis of different types of lesion.

[Contrast-enhanced ultrasonography for detecting testicular perfusion in acute testis contusion in rabbits].

OBJECTIVE: To evaluate contrast-enhanced ultrasonography (CEUS) in detecting testicular perfusion in acute testis contusion. METHODS: We established the model of testis contusion in 11 healthy male New Zealand rabbits by randomly hitting one side of the scrotum under general anesthesia. We examined the bilateral scrotums of all the animals before, immediately after and at 2, 4 and 6 hours after modeling by color Doppler flow imaging (CDFI) and CEUS, and analyzed the time-intensity curve (TIC), arriving time (AT), time to peak intensity (TTP), peak intensity (PI), half time of descending peak intensity (HT) and area under the curve (AUC) in the healthy and injured testis, respectively. RESULTS: CEUS exhibited a higher sensitivity in detecting tissue perfusion than CDFI. The mode of contrast agent perfusion in testicular contusion was fast in and slow out. There were no evident differences between the contused and the healthy testis in AT, TTP and PI before modeling. The contused testis showed significantly earlier AT and TTP, higher PI and larger AUC (P < 0.05) than the healthy one at different time points after modeling, but no statistically significant difference was found in HT (P > 0.05). CONCLUSION: Accurate parameters of testicular perfusion in acute testis contusion can be quantitatively obtained by CEUS, which are of important value for the diagnosis of testis contusion.

[Contrast-enhanced ultrasonography in the diagnosis of acute experimental incomplete testicular torsion].

OBJECTIVE: To explore the application value of contrast-enhanced ultrasonography (CEUS) in the diagnosis of acute experimental incomplete testicular torsion. METHODS: Seven incomplete and 1 complete testicular torsion models were established in 8 healthy hybrid dogs by twisting unilateral spermatic cord. The twisted testes were included in the model group and the healthy ones in the control. All the dogs underwent CEUS before, immediately after, and/or 6 hours after the torsion, followed by time-intensity curve analysis. RESULTS: The arriving time (AT) and the time to peak (TTP) of the contrast agents in the bilateral testes were almost coincident, and the peak intensity (PI) and the area under the curve (AUC) in the bilateral testes basically the same before the torsion. The incompletely torsion testes showed delayed perfusion of contrast agents, prolonged AT and 'TP, and decreased PI and AUC as compared with the contralateral testes (P < 0.05), while the completely torsion one exhibited no perfusion all the time. CONCLUSION: CEUS has a very high application value in the diagnosis of acute incomplete testicular torsion.