Radioactive Hydroxyapatite Microspheres Empower Sustainable In Situ Tumor Vaccination.

Tumor in situ vaccination (ISV) strategies have emerged in clinical trials as promising approaches, involving the release of tumor antigens through local radiotherapy and intratumorally adjuvant injections. However, the current fabrication strategy for achieving a sustainable immune response to ISV remains a pressing challenge. In this study, we present an empowered sustainable ISV method for antitumor therapy using 177Lu-labeled manganese-doped mesoporous hydroxyapatite (177Lu/Mn-HAP) microspheres. The ISV enables the sustained utilization of tumor antigens, leading to the activation of dendritic cells and polarization of macrophages toward the M1 subtype. Consequently, it facilitates the generation of potent CD8+ T-cell responses, enhancing the antitumor effects of internal radiation in both primary and distant tumors. Importantly, this approach achieves complete remission in all tumor-bearing mice and stimulates immune memory to prevent tumor recurrence. Our study highlights a universal and safe ISV strategy capable of inducing potent tumor-specific and sustainable immune response.

Radioresponsive Delivery of Toll-like Receptor 7/8 Agonist for Tumor Radioimmunotherapy Enabled by Core-Cross-Linked Diselenide Nanoparticles.

The development of a radioresponsive delivery platform has led to an innovative combination radioimmunotherapy strategy for treating tumors. However, controlling the release of immunomodulators by local radiotherapy in vivo remains a significant challenge in order to minimize off-target toxicity, reduce radiation-induced immunosuppression, and maximize synergistic radioimmunotherapy efficacy. In this study, we report the development of core-cross-linked diselenide nanoparticles (dSeNPs) as carriers for radioresponsive delivery of the toll-like receptors 7/8 agonist through systemic administration to achieve combined radioimmunotherapy of tumors. The dSeNPs were fabricated from a ring-opening reaction between 2,2'-diselenidebis(ethylamine) and the ethylene oxide group of an amphiphilic block copolymer. The diselenide bonds were naturally protected in the core of the self-assembled nanostructure, making the dSeNPs extremely stable in the physiological environment. However, they exhibited dose- and time-dependent radiosensitivity, meaning that X-ray irradiation could spatiotemporally control the release of R848 from the dSeNPs. In vivo results showed that local radioresponsive R848 release from dSeNPs greatly improved the synergistic efficacy of combined radioimmunotherapy via the programmed cooperative immune system activation process. This process included macrophage polarization, dendritic cell maturation, and cytotoxic T cell activation. Our findings suggest that core-cross-linked dSeNPs are a promising platform for combined radiotherapy due to their spatiotemporal controllability of radioresponsive drug release.

Radiotherapy-Triggered In Situ Tumor Vaccination Boosts Checkpoint Blockaded Immune Response via Antigen-Capturing Nanoadjuvants.

In situ vaccination (ISV) formed with the aid of intratumorally injected adjuvants has shed bright light on enhancing the abscopal therapeutic effects of radiotherapy. However, the limited availability of antigens resulting from the radiotherapy-induced immunogenic cell death largely hampers the clinical outcome of ISV. To maximally utilize the radiotherapy-induced antigen, we herein developed a strategy by capturing the radiotherapy-induced antigen in situ with a nanoadjuvant comprised of CpG-loaded Fe3O4 nanoparticles. The highly efficient click reaction between the maleimide residue on the nanoadjuvant and sulfhydryl group on the antigen maximized the bioavailability of autoantigens and CpG adjuvant in vivo. Importantly, combined immune checkpoint blockade can reverse T cell exhaustion after treatment with radiotherapy-induced ISV, thereby largely suppressing the treated and distant tumor. Mechanistically, metabolomics reveals the intratumorally injected nanoadjuvants disrupt redox homeostasis in the tumor microenvironment, further inducing tumor ferroptosis after radiotherapy. Overall, the current study highlights the immense potential of the innovative antigen-capturing nanoadjuvants for synergistically enhancing the antitumor effect.

Automatic segmentation of the female pelvic floor muscles on MRI for pelvic floor function assessment.

Background: Pelvic organ prolapse (POP) is a pelvic floor dysfunction disease which affects females. The volume of pelvic floor muscle, especially the levator ani muscle (LAM), is an important indicator of pelvic floor function. However, muscle volume measurements depend on manual segmentation, which is clinically time-consuming. In this work, we present an efficient automatic segmentation model of pelvic floor muscles with magnetic resonance imaging (MRI) based on DenseUnet, to achieve muscle volume calculation and provide a reference for the assessment of pelvic floor function. Methods: A total of 49 female pelvic floor magnetic resonance (MR) series were retrospectively enrolled from the First Affiliated Hospital of Army Military Medical University between 2013 and 2021, including 21 normal participants and 28 patients with stage 1-4 POP. The LAM, internal obturator muscle (IOM), and external anal sphincter (EAS) were manually segmented. An improved DenseUnet was proposed for automatic segmentation of these 3 muscles. The Dice similarity coefficient (DSC), Hausdorff distance (HD), and average symmetrical surface distance (ASSD) were used to evaluate segmentation results. The segmentation performance of the improved DenseUnet was compared with those of standard DenseUnet, ResUnet, Unet++, and Unet. Results: The improved DenseUnet showed a good performance. The average DSC and standard deviation of the LAM, IOM, and EAS was 0.758±0.151, 0.716±0.173, and 0.810±0.147, respectively. The average HD was 22.41, 19.00, and 36.01 mm, respectively; and the average ASSD was 3.66, 3.80, and 5.23 mm, respectively. The average DSC and standard deviation of the normal group and POP group was 0.779±0.166 and 0.757±0.154, respectively. There was no significant difference between the muscle volume of the improved DenseUnet and manual segmentation (all P values >0.05). The average total segmentation time for 1 case was 10.18 s on our setup, which is much lower than the manual segmentation time of 45 minutes. Conclusions: The improved DenseUnet segments the pelvic floor muscles in MRI quickly and efficiently, with good precision and faster speed than those of manual segmentation. This can assist doctors in quickly segmenting pelvic floor muscles, calculating muscle volume, and further evaluating pelvic floor function.

Targeting STING Activation by Antigen-Inspired MnO2 Nanovaccines Optimizes Tumor Radiotherapy.

Immune checkpoint blockers therapy can improve the radiotherapy-induced immunosuppression by enhancing interferon secretion, but still suffer from low clinical response rate and potential adverse effects. Mn2+ -mediated activation of interferon gene stimulator (STING) pathway provides an alternative for combination radioimmunotherapy of tumor. However, it is still a challenge for specific delivery of Mn2+ to innate immune cells and targeting activation of STING pathway. Herein, a novel antigen-inspired MnO2 nanovaccine is fabricated as Mn2+ source and functionalized with mannose, enabling it to target innate immune cells to activate the STING pathway. Meanwhile, the release of Mn2+ in the intracellular lysosomes can also be for magnetic resonance imaging to monitor the dynamic distribution of nanovaccines in vivo. The targeting activation of STING pathway can enhance radiotherapy-induced immune responses for inhibiting local and distant tumors, and resisting tumor metastasis. The study proposes an optimized radiotherapy strategy through targeting STING activation of antigen-inspired nanovaccines.

Chemotherapy-Sensitized In Situ Vaccination for Malignant Osteosarcoma Enabled by Bioinspired Calcium Phosphonate Nanoagents.

How to effectively treat malignant osteosarcoma remains clinically challenging. Programmed delivery of chemotherapeutic agents and immunostimulants may offer a universal strategy for killing osteosarcoma cells while simultaneously eliciting in situ antitumor immunity. However, targeted chemoimmunotherapy lacks a reliable delivery system. To address this issue, we herein developed a bioinspired calcium phosphonate nanoagent that was synthesized by chemical reactions between Ca2+ and phosphonate residue from zoledronic acid using bovine serum albumin as a scaffold. In addition, methotrexate combination with a phosphorothioate CpG immunomodulator was also loaded for pH-responsive delivery to enable synergistic chemoimmunotherapy of osteosarcoma. The calcium phosphonate nanoagents were found to effectively accumulate in osteosarcoma for nearly 1 week, which is favorable for exerting the vaccination effects in situ by maturing dendritic cells and priming CD8+ T cells to suppress the osteosarcoma progression and pulmonary metastasis through controlled release of the three loaded agents in the acidic tumor microenvironment. The current study may thus offer a reliable delivery platform for achieving targeted chemotherapy-induced in situ antitumor immunity.

Fibrinogen/poly(l-lactide-co-caprolactone) copolymer scaffold: A potent adhesive material for urethral tissue regeneration in urethral injury treatment.

Since a scarcity of sufficient grafting materials, several complications can arise after urothelial defect reconstruction surgery, including severe hypospadias. Accordingly, developing alternative therapies, such as urethral restoration via tissue engineering are needed. In the present study, we developed a potent adhesive and repairing material using fibrinogen-poly(l-lactide-co-caprolactone) copolymer (Fib-PLCL) nanofiber scaffold to achieve effective urethral tissue regeneration after seeding with epithelial cells on the surface. The in vitro result found the Fib-PLCL scaffold promoted the attachment and viability of epithelial cells on their surface. The increased expression levels of cytokeratin and actin filaments were observed in Fib-PLCL scaffold than PLCL scaffold. The in vivo urethral injury repairing potential of Fib-PLCL scaffold was evaluated using a rabbit urethral replacement model. In this study, a urethral defect was surgically excised and replaced with the Fib-PLCL and PLCL scaffolds or autograft. As expected, the animals healed well after surgery in the Fib-PLCL scaffold group, and no significant strictures were identified. As expected, the cellularized Fib/PLCL grafts have induced the luminal epithelialization, urethral smooth muscle cell remodelling, and capillary development all at the same time. Histological analysis revealed that the urothelial integrity in the Fib-PLCL group had progressed to that of a normal urothelium, with enhanced urethral tissue development. Based on the results, the present study suggests that the prepared fibrinogen-PLCL scaffold is more appropriate for urethral defect reconstruction.

Gadolinium-Bisphosphonate Nanoparticle-Based Low-Dose Radioimmunotherapy for Osteosarcoma.

Osteosarcoma is a malignant osteogenic tumor with a high metastatic rate commonly occurring in adolescents. Although radiotherapy is applied to treat unresectable osteosarcoma with radiation resistance, a high dose of radiotherapy is required, which may weaken the immune microenvironment. Therefore, there is an urgent need to develop novel agents to maximize the radiotherapeutic effects by eliciting immune activation effects. In this study, we synthesized therapeutic gadolinium-based metal-bisphosphonate nanoparticles (NPs) for osteosarcoma treatment that can be combined with radiotherapy. The gadolinium ion (Gd) was chelated with zoledronic acid (Zol), a commonly used drug to prevent/treat osteoporosis or bone metastases from advanced cancers, and stabilized by ovalbumin (OVA) to produce OVA-GdZol NPs. OVA-GdZol NPs were internalized into K7M2 osteosarcoma cells, showing a high sensitization effect under X-ray irradiation. Cell pretreatment of OVA-GdZol NPs significantly enhanced the radiation therapeutic effect in vitro by reducing the cell colonies and increased the signal of γH2AX-positive cells. More importantly, OVA-GdZol NPs promoted the maturation of bone marrow-derived dendritic cells (BMDCs) and M1 polarization of macrophages. The inhibitory effect on K7M2 osteosarcoma of OVA-GdZol NPs and X-ray radiation was evident, indicated by a significantly reduced tumor volume, high survival rate, and decreased lung metastasis. Meanwhile, both innate and adaptive immune systems were activated to exert a strong antitumor effect. The above results highly suggest that OVA-GdZol NPs serve as both radiosensitizers and immune adjuvants, suitable for the sequential combination of vaccination and radiotherapy.

Injectable pH-responsive hydrogel for combinatorial chemoimmunotherapy tailored to the tumor microenvironment.

Although combination chemoimmunotherapy shows promising clinical results for cancer treatment, this approach is largely restricted by variable objective response rate and severe systemic adverse effects of immunotherapeutic antibody and chemotherapeutic drugs. Therefore, an in situ-formed therapeutic silk-chitosan composite scaffold is fabricated in this study to allow local release of the chemotherapeutic drug doxorubicin (DOX) and JQ1 (small molecular inhibitor used for the extraterminal protein BRD4 and bromodomain) with control release kinetics. DOX-JQ1@Gel contains a pH-degradable group that releases therapeutics in a weak acidic tumor microenvironment. The released DOX could directly kill tumor cells or lead to immunogenic cell death, thereby triggering the response of antitumor immunity. Meanwhile, chemotherapy-triggered antigen release and JQ1-mediated PD-L1 checkpoint blockade cumulatively contribute to trigger the response of antitumor immunity. Finally, the DOX-JQ1@Gel is locally injected to evaluate its synergistic cancer therapeutic effect, which is expected to improve objective response rate of immunotherapy and minimize systemic side effects.

Potential biomarkers and the molecular mechanism associated with DLL4 during renal cell carcinoma progression.

BACKGROUND: Delta-like canonical notch ligand 4 (DLL4) is considered a potential prognostic gene for renal cell carcinoma (RCC). We assessed the molecular mechanisms and novel biomarkers associated with DLL4 during RCC development. METHODS: Four gene expression profiles were downloaded from the GEO database. Differentially expressed genes (DEGs) were identified between RCC and normal renal samples, including common DEGs (co-DEGs). Thereafter, RCC-associated gene exploration was performed and a PPI network was constructed to identify the core genes. Survival analysis of core genes in the high expression group (H group) and low expression group (L group) was also performed. The key genes related to the core genes were investigated, and the miRNA-target genes and TFs-target genes were analyzed. Finally, the expression levels of VEGFA, FLT1, EGLN3, and DLL4 in RCC and paracancerous tissues were determined. RESULTS: A total of 11,867 DEGs and 622 co-DEGs were identified in this study, and 67 RCC-associated genes that were mainly enriched in signal transduction and angiogenesis function were further explored. VEGFA was identified as the core gene. Further, 30 DEGs and 9 DE-miRNAs were identified between the H and L groups. VEGFA was positively correlated with 19 genes, including EGLN3, FLT1, and DLL4. A total of 18 miRNA-target interactions, including miR-134-5p-DLL4, were obtained. VEGFA, FLT1, EGLN3, and DLL4 were significantly expressed in RCC tissues compared with paracancerous tissues. CONCLUSIONS: DLL4 may contribute to the development of RCC by participating in signal transduction and angiogenesis. VEGFA, FLT1, EGLN3, DLL4, and miR-134-5p may be novel biomarkers for RCC.

Efficacy of Yougui pill combined with Buzhong Yiqi decoction in alleviating the sexual dysfunction in female rats through modulation of the gut microbiota.

CONTEXT: Yougui pill combined with Buzhong Yiqi decoction (YPBYD) is used to relieve sexual dysfunction in clinical practice. OBJECTIVE: To investigate changes in microbial composition caused by sexual dysfunction and identify dominant bacteria related to YPBYD treatment. MATERIALS AND METHODS: Female Sprague-Dawley rats were randomly divided into four groups (n = 6): one group underwent Sham operation (Sham group), while three groups underwent ovariectomy (one model and two treatment groups). The ovariectomized (OVX) rats received oestradiol benzoate (250 µg/kg/week) or YPBYD (3.6 mL/d) via oral gavage for 4 weeks. Vaginal smear assay was performed; the serum levels of cyclic adenosine monophosphate (cAMP) and oestradiol (E2) were measured, followed by collection of stool samples for 16S rRNA sequencing. RESULTS: After YPBYD treatment, the levels of E2 and cAMP in OVX rats significantly increased (E2: from 20.45 ± 1.60 ng/L to 24.38 ± 1.70 ng/L; cAMP: from 261.41 ± 9.21 pg/mL to 373.75 ± 17.37 pg/mL). OVX treatment decreased diversity of gut microbiota and YPBYD treatment restored gut microbiota composition. Compared with Sham group, the abundance of Romboutsia significantly increased, while those of Proteobacteria and Staphylococcus markedly decreased in OVX group (all p < 0.05); meanwhile, the abundance of these microbes showed an opposite trend after YPBYD treatment. These microbiotas were involved in tyrosine and tryptophan biosynthesis and fatty acid metabolism. DISCUSSION AND CONCLUSIONS: These findings are the first to indicate YPBYD can alleviate female sexual dysfunction by modulating gut microbiota in OVX rats, which will help enhance the understanding on potential mechanism of YPBYD against sexual dysfunction.

[Effects of 1470 nm semiconductor laser vaporization of the prostate on erectile function and pelvic floor muscle strength in patients with benign prostatic hyperplasia].

OBJECTIVE: To study the effects of 1470 nm semiconductor laser enucleation of the prostate (SCLEP) and transurethral plasma electrotomy (TUPE) on erectile function and pelvic floor muscle strength in BPH patients. METHODS: We retrospectively analyzed the clinical data on 72 cases of BPH treated in our hospital from July 2017 to July 2019 by TUPE (group A, n = 36) or 1470 nm SCLEP (group B, n = 36). We observed and compared the postoperative penile erectile function, retrograde ejaculation and pelvic floor muscle strength between the two groups of patients. RESULTS: Compared with group A, group B showed a significantly higher IIEF-5 score (19.43 ± 1.61 vs 21.15 ± 1.32, P < 0.05) and pelvic floor muscle strength (electromyographic ï¼»EMGï¼½ value) during rapid contraction (36.36 ± 1.38 vs 43.53 ± 2.04, P < 0.05), continuous contraction (34.27 ± 1.63 vs 39.46 ± 1.48, P < 0.05) and endurance test (35.24 ± 1.57 vs 38.19 ± 1.67, P < 0.05), but lower incidence rates of ED and retrograde ejaculation. CONCLUSIONS: Compared with TUPE, 1470 nm SCLEP affects less the erectile function and pelvic floor muscle strength of BPH patients.

Efficacy of Yun-Type Optimized Pelvic Floor Training Therapy for Middle-Aged Women With Severe Overactive Bladder: A Randomized Clinical Trial.

Background: This study aimed to evaluate the clinical efficacy of Yun-type optimized pelvic floor training therapy for middle-aged women with severe overactive bladder (OAB). Methods: This randomized, observer-blinded, parallel-group controlled clinical trial included 108 middle-age women with severe OAB and assigned them to the intervention group (treated with combination of Yun-type optimized pelvic floor training with solifenacin for 12 weeks) and control group (treated with solifenacin for 6 weeks and, after 2 weeks of elution, received the combination of Yun-type optimized pelvic floor training and solifenacin for 6 weeks). The outcomes associated with OAB, pelvic floor muscle (PFM) function, and sexual function were compared after 6 and 12/14 weeks of treatment. Results: The primary variables were OAB-associated outcomes, including overactive bladder symptom score (OABSS), urgent urination, urine, nocturia, urge urinary incontinence, patient's perception of bladder condition, urogenital distress inventory-6, incontinence impact questionnaire-7, voiding volume, average flow rate, and maximum flow rate. The secondary variables were indicators related to PFM function and sexual function. These indicators were significantly improved in both groups after interventions. Notably, the improvements in most of these indicators were superior in the intervention group than in the control group after 6 weeks and 12/14 weeks of treatment. Conclusions: The use of Yun-type optimized pelvic floor training adds to the benefits of solifenacin regarding severe OAB-associated outcomes, PMF function, and sexual function in middle-aged women with severe OAB. Combining Yun-type optimized pelvic floor training with traditional drug therapies may improve clinical outcomes in patients with severe OAB. Trial Registration: ChiCTR-INR-17012189.

Surface PEGylated Cancer Cell Membrane-Coated Nanoparticles for Codelivery of Curcumin and Doxorubicin for the Treatment of Multidrug Resistant Esophageal Carcinoma.

OBJECTIVE: The emergence of multi-drug resistance (MDR) in esophageal carcinoma has severely affected the effect of chemotherapy and shortened the survival of patients. To this end, we intend to develop a biomimetic nano-targeting drug modified by cancer cell membrane, and investigate its therapeutic effect. METHODS: The degradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with doxorubicin (DOX) and curcumin (Cur) were prepared by solvent evaporation method. TE10 cell membrane and Distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-PEG) were then coated on the PLGA NPs by membrane extrusion to prepare the PEG-TE10@PLGA@DOX-Cur NPs (PMPNs). Size and zeta potential of the PMPNs were analyzed by lazer particle analyzer, and the morphology of PMPNs was observed by transmission electron microscope. The TE10 cell membrane protein on PMPNs was analyzed by gel electrophoresis. The DOX-resistant esophageal cancer cell model TE10/DOX was established through high-dose induction. The In vitro homologous targeting ability of PMPNs was evaluated by cell uptake assay, and the in vitro anti-tumor effect of PMPNs was assessed through CCK-8, clone formation and flow cytometry. A Balb/c mouse model of TE10/DOX xenograft was constructed to evaluate the anti-tumor effect in vivo and the bio-safety of PMPNs. RESULTS: The prepared cell membrane coated PMPNs had a regular spherical structure with an average diameter of 177 nm. PMPNs could directly target TE10 and TE10/DOX cells or TE10/DOX xenografted tumor and effectively inhibit the growth of DOX-resistant esophageal carcinoma. Besides, the PMPNs was confirmed to have high biosafety. CONCLUSION: In this study, a targeted biomimetic nano-drug delivery system PMPNs was successfully prepared, which overcome the MDR of esophageal carcinoma by co-delivering DOX and sensitizer curcumin.

Apoferritin-Engineered Nanoprobe for Tumor-Targeted Triple-NIR Imaging and Phototherapy.

Considering that pathological hallmarks are directly related to structural and chemical information of tumor, noninvasive, real-time, spatially resolved quantitative chemical imaging is significant for treatment decisions. The discovery of the transparency window of biological tissues and the advancement of near-infrared technology provide exciting prospects for in vivo imaging. Herein, an engineering apoferritin-conjugated cypate nanoprobe is fabricated for near-infrared photoacoustic imaging and fluorescence imaging in the first and second window. As the analogue of indocyanine green, dicarboxylic cypate is directly conjugated with the apoferritin molecules for forming assembly nanoprobes. Resulting from the intrinsic targeting and optical capacity of the nanoprobes, the triple near-infrared imaging can perform multimeasurements of the target analyte in real-time. This imaging methodology not only provides the structural background information of the tumor, each pixel also contains quantitative in situ information of the tumor. In particular, part of the absorbed light energy is released as heat energy in the near-infrared photoacoustic imaging process. The constructed triple near-infrared nanoprobes therefore naturally navigate the photothermal treatment plan of tumor and finally realize the efficient assistance of tumor photothermal ablation. The tumor metabolomics reveal that the nanoprobe-assisted tumor ablation has a potential mechanism toward glutamine- and phenylalanine-related metabolism perturbation and the disordered oxidative stress state. The tumor-specific bioconjugate nanoprobes hold great potential as a versatile theranostic platform for tumor imaging and therapy.

Hepatotoxicity of copper sulfide nanoparticles towards hepatocyte spheroids using a novel multi-concave agarose chip method.

Aim: To explore the hepatotoxicity of copper sulfide nanoparticles (CuSNPs) toward hepatocyte spheroids. Materials & methods: Other than the traditional agarose method to generate hepatocyte spheroids, we developed a multi-concave agarose chip (MCAC) method to investigate changes in hepatocyte viability, morphology, mitochondrial membrane potential, reactive oxygen species and hepatobiliary transporter by CuSNPs. Results: The MCAC method allowed a large number of spheroids to be obtained per sample. CuSNPs showed hepatotoxicity in vitro through a decrease in spheroid viability, albumin/urea production and glycogen deposition. CuSNPs also introduced hepatocyte spheroid injury through alteration of mitochondrial membrane potential and reactive oxygen species, that could be reversed by N-acetyl-l-cysteine. CuSNPs significantly decreased the activity of BSEP transporter by downregulating its mRNA and protein levels. Activity of the MRP2 transporter remained unchanged. Conclusion: We observed the hepatotoxicity of CuSNPs in vitro with associated mechanisms in an advanced 3D culture system.

Iodinated BSA Nanoparticles for Macrophage-Mediated CT Imaging and Repair of Gastritis.

The development of a specific and noninvasive technology for understanding gastritic response together with efficient therapy is an urgent clinical issue. Herein, we fabricated a novel iodinated bovine serum albumin (BSA) nanoparticle based on gastritic microenvironment for computed tomography (CT) imaging and repair of acute gastritis. Derived from the characteristic mucosa defect and inflammatory cell (e.g., macrophage and neutrophil) infiltration in acute gastritis, the pH-sensitive nanoparticles can sedimentate under acidic conditions and be uniformly distributed in the defected mucosal via the phagocytosis of inflammatory cells. Hence, enhanced CT images can clearly reveal the mucosal morphology in the nanoparticle-treated gastritic rat over a long time window comparison with nanoparticle-treated healthy rats and clinical small-molecule-treated gastritic rat. In addition, we have discovered that nanoparticles can repair the atrophic gastric mucosa to a normal state. This repair process mainly stems from inflammatory immune response caused by phagocytized nanoparticles, such as the polarization of proinflammatory macrophages (M1) to anti-inflammatory macrophages (M2). The biocompatible nanoparticles that avoid the inherent defects of the clinical small molecules have great potential for accurate diagnosis and treatment of gastritis in the early stage.

The Correlation between Severity of Overactive Bladder Symptoms with Female Sexual Dysfunction and Sexual Satisfaction of Partners.

PURPOSE: Sexual dysfunction in women with overactive bladder (OAB) syndrome has been an important topic, while the sexual satisfaction of partners has not been fully investigated. Our aim was to explore the association between the severity of OAB with female sexual dysfunction and sexual satisfaction of partners. METHODS: A total of 323 patients with OAB recruited in our hospital were included in our study from September 2017 to March 2019. Data were collected by Overactive Bladder Symptom Score (OABSS) questionnaire, self-designed questionnaire for basic characteristics; Female Sexual Function Index (FSFI); and sexual satisfaction survey for sex partners of patients. χ2 test or 1-way ANOVA was used to compare the variables among groups. Logistic regression analysis was performed to analyze the severity of OAB with female sexual dysfunction and sexual satisfaction of partners. The correlations between different OABSS domains with female sexual dysfunction and sexual satisfaction of partners were assessed. RESULTS: All the patients were classified into mild (n = 107), moderate (n = 98), severe (n = 118) OAB group based on OABSS. Most of the basic information were similar among groups, except for BMI, highest education, occupation, fertility, and history of pelvic floor surgery. After multiple factors correction, the severity of OAB, exercise frequency, and the history of pelvic floor surgery were statistically associated with the female sexual dysfunction and sexual satisfaction of partners. Urgency score was significantly correlated with female sexual dysfunction, and the urge incontinence was most significantly associated with the sexual satisfaction of partners. CONCLUSION: Severe OAB was closely associated with female sexual dysfunction and sexual satisfaction of partners. The urgency and urge incontinence should be focused for OAB management.

[Application value of a metamorphic mechanism-based special dressing system for patients after scrotal surgery].

OBJECTIVE: To investigate the application of a metamorphic mechanism-based special dressing system (MMDS) in improving the prognosis and comfort of the patient after scrotal surgery. METHODS: We included 48 cases of scrotal surgery using the traditional method for postoperative dressing from June 2017 to June 2018 (the control group) and another 48 cases employing MMDS postoperatively from July 2018 to June 2019 (the MMDS group). We observed the differences between the two groups of patients in the incidence of scrotal edema, pain score, hospitalization days, patients' satisfaction, and dressing time. RESULTS: The scrotal edema score showed no statistically significant difference between the MMDS and control groups at 24 hours after operation (P > 0.05) but remarkably lower in the former than in the latter group at 48 hours (1.42 ± 0.5 vs 2.27 ± 0.7, P < 0.05) and 72 hours postoperatively (1.35 ± 0.2 vs 2.25 ± 0.7, P < 0.05). The MMDS group, compared with the controls, also exhibited a lower pain score (2.2 ± 1.0 vs 3.4 ± 1.5, P < 0.05), shorter hospitalization time (ï¼»5.96 ± 1.2ï¼½ vs ï¼»9.13 ± 2.3ï¼½ d, P < 0.05) and higher satisfaction score (98.1 ± 1.6 vs 92.8 ± 2.8, P < 0.05), as well as shorter dressing time at 24, 48 and 72 hours after operation (P < 0.05). CONCLUSIONS: The metamorphic mechanism-based special dressing system is a safe, efficient, simple and feasible method for dressing after scrotal surgery, which can effectively promote recovery and improve the quality of life of the patients.

Bone-Seeking Albumin-Nanomedicine for In Vivo Imaging and Therapeutic Monitoring.

Malignant osteolysis associated with irreversible primary bone tumors and bone metastases remains a clinically urgent problem. Exploiting the imaging and therapy function of flexible nanomedicine can provide an alternative for therapeutic navigation and monitoring of malignant osteolysis. Here, we report the development of albumin-based gadolinium oxide nanoparticles loaded with doxorubicin and conjugated with bone-seeking alendronate for targeted delivery and therapeutic monitoring. Compared with nontargeted nanomedicine, bone-seeking accumulation and retention can be proven by MRI in a rat model of focal malignant osteolysis. Meanwhile, we observed a whole-body distribution in the consecutive SPECT imaging after radiolabeling with 125I, SPECT imaging also indicated the enhanced bone tumor accumulation and prolonged retention. Resulting from the high drug loading and 131I labeling efficiency, the targeted nanomedicine exhibited significant chemotherapy and inter-radiotherapy capacity. Ultimately, the tumor burden of rats was obviously decreased except for the nontargeted group and the empty carrier group. In vivo CT imaging and pathological analysis revealed that the combined therapy was an efficient measure for antiosteolysis. Our findings suggest that albumin-based nanomedicine can provide a platform for bone-seeking diagnosis and therapeutic monitoring.