A critical assessment of clustering algorithms to improve cell clustering and identification in single-cell transcriptome study.

Cell clustering is typically the initial step in single-cell RNA sequencing (scRNA-seq) analyses. The performance of clustering considerably impacts the validity and reproducibility of cell identification. A variety of clustering algorithms have been developed for scRNA-seq data. These algorithms generate cell label sets that assign each cell to a cluster. However, different algorithms usually yield different label sets, which can introduce variations in cell-type identification based on the generated label sets. Currently, the performance of these algorithms has not been systematically evaluated in single-cell transcriptome studies. Herein, we performed a critical assessment of seven state-of-the-art clustering algorithms including four deep learning-based clustering algorithms and commonly used methods Seurat, Cosine-based Tanimoto similarity-refined graph for community detection using Leiden's algorithm (CosTaL) and Single-cell consensus clustering (SC3). We used diverse evaluation indices based on 10 different scRNA-seq benchmarks to systematically evaluate their clustering performance. Our results show that CosTaL, Seurat, Deep Embedding for Single-cell Clustering (DESC) and SC3 consistently outperformed Single-Cell Clustering Assessment Framework and scDeepCluster based on nine effectiveness scores. Notably, CosTaL and DESC demonstrated superior performance in clustering specific cell types. The performance of the single-cell Variational Inference tools varied across different datasets, suggesting its sensitivity to certain dataset characteristics. Notably, DESC exhibited promising results for cell subtype identification and capturing cellular heterogeneity. In addition, SC3 requires more memory and exhibits slower computation speed compared to other algorithms for the same dataset. In sum, this study provides useful guidance for selecting appropriate clustering methods in scRNA-seq data analysis.

Comparative study of female pelvic floor among undeformed high-resolution thin-sectional anatomical (visible human) images and MRI and ultrasound images.

PURPOSE: Using visible human, MRI and ultrasound images, we aim to provide an anatomical basis for the identification and diagnosis of pelvic floor structure and disease by ultrasound imaging. METHODS: One Chinese visible human (CVH) image, one American visible human image, 9 MRI images of normal volunteers, and 40 ultrasound images of normal volunteers or pelvic organ prolapse patients were used. Pelvic organs, pelvic floor muscles, and the connective tissue in CVH, VHP, MRI, and ultrasound images were selected for comparative study. RESULTS: We successfully identified the boundary of the anal sphincter complex, including the subcutaneous, superficial, and deep parts of the external anal sphincter, conjoined longitudinal muscles and internal anal sphincter; the levator ani muscle (LAM), including the internal and external parts of the pubovisceral muscle and the superficial and deep parts of the puborectal muscle; the urethral sphincter complex, including the urethral sphincter proper and the urethral compressor; and the perineal body, the rectoperineal muscle and superficial transverse perineal muscle. CONCLUSIONS: We successfully recognized and studied the location, subdivisions, 2D morphology and spatial relationships of the LAM, anal sphincter complex, urethral sphincter complex and perineal body in ultrasound images, thereby helping sonologists or clinicians accurately identify pelvic floor muscles and supporting structures in ultrasound images.

[Multiple precision behavioral therapy for mild to moderate stress urinary incontinence with sexual dysfunction in women].

OBJECTIVE: To explore the clinical effect of multiple precision behavioral therapy (MPBT) on mild to moderate stress urinary incontinence (SUI) with female sexual dysfunction (FSD) in women. METHODS: We randomly divided 90 female patients with mild to moderate SUI with FSD into three groups of an equal number: control group A, control group B and an MPBT group, treated by electrical stimulation, Kegel training and MPBT, respectively, all for 8 weeks. Using International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), Incontinence Impact Questionnaire (IIQ-7), Female Sexual Function Indexes (FSFI) and Glazer protocol, we evaluated the clinical effects, recorded the cost of treatment, and compared them among the three groups of patients. RESULTS: Totally, 87 of the patients completed the treatment, 27 in control group A, 30 in control group B and 30 in the MPBT group. There was no significant difference in the baseline data among the three groups (P > 0.05). ICIQ-SF and IIQ-7 scores, FSFI and Glazer values were remarkably improved in the MPBT group after treatment (P < 0.05). The therapeutic effect was significantly better and the treatment cost markedly lower in the MPBT than in the control groups (P < 0.05). CONCLUSION: Multiple precision behavioral therapy can effectively improve the clinical symptoms of mild to moderate stress urinary incontinence and sexual dysfunction in women, with low cost and high safety.

[Effect of functional acupoint electrical stimulation combined with tadalafil on erectile dysfunction in middle-aged and elderly patients].

OBJECTIVE: To investigate the application effect of functional acupoint electrical stimulation combined with tadara irregular administration in middle-aged and elderly patients with erectile dysfunction (ED), and to provide reference for clinical treatment. METHODS: A total of 40 middle-aged and elderly patients with ED admitted to the pelvic floor Center of our hospital from March 2021 to March 2023 were randomly divided into two groups with 20 cases in each group.The control group was treated with tadalafil regularly, and the observation group was treated with functional acupoint electrical stimulation on the basis of this treatment. The total course of treatment was 6 weeks.The clinical efficacy of the two groups was compared. The therapeutic efficacy was evaluated by the International Erectile Function Index (IIEF-5), penile hardness score (EHS), serum total testosterone (TT) level, sexual satisfaction scale (SS) and pelvic floor electromyography, and the occurrence of adverse events was recorded. RESULTS: The total effective rate of the observation group was significantly higher than that of the control group (90% vs 70%, P < 0.05). After 6 weeks of treatment, both groups showed improvements in IIEF-5, EHS, SS, and TT compared to before treatment (P < 0.01). However, the improvement in the observation group was significantly better than that in the control groupï¼»IIEF-5: (22.13±2.11) vs (19.69±2.04), EHS: (3.68±0.47) vs (2.89±0.60), SS: (77.41±7.59) vs (70.32±7.28), TT: (13.43±3.89) nmol/L vs (8.85±3.02) nmol/L, all P < 0.01ï¼½; There were no significant changes in pelvic floor muscle electromyography values in the control group before and after treatment (P > 0.05), while in the observation group, pelvic floor muscle electromyography values (PFMV) in the pre-resting phase, fast muscle (Type II muscle) phase, slow muscle (Type I muscle) phase, endurance testing phase, and post-resting phase all improved compared to before treatment and were superior to the control group (P < 0.05). CONCLUSION: Functional acupoint electrical stimulation combined with tadara irregular administration can improve the therapeutic effect of middle-aged and elderly patients with ED, improve pelvic floor function, safe and reliable.

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.

Preclinical safety and hepatotoxicity evaluation of biomineralized copper sulfide nanoagents.

Albumin-biomineralized copper sulfide nanoparticles (Cu2-xS NPs) have attracted much attention as an emerging phototheranostic agent due to their advantages of facile preparation method and high biocompatibility. However, comprehensive preclinical safety evaluation is the only way to meet its further clinical translation. We herein evaluate detailedly the safety and hepatotoxicity of bovine serum albumin-biomineralized Cu2-xS (BSA@Cu2-xS) NPs with two different sizes in rats. Large-sized (LNPs, 17.8 nm) and small-sized (SNPs, 2.8 nm) BSA@Cu2-xS NPs with great near-infrared absorption and photothermal conversion efficiency are firstly obtained. Seven days after a single-dose intravenous administration, SNPs distributed throughout the body are cleared primarily through the feces, while a large amount of LNPs remained in the liver. A 14-day subacute toxicity study with a 28-day recovery period are conducted, showing long-term hepatotoxicity without recovery for LNPs but reversible toxicity for SNPs. Cellular uptake studies indicate that LNPs prefer to reside in Kupffer cells, leading to prolonged and delayed hepatotoxicity even after the cessation of NPs administration, while SNPs have much less Kupffer cell uptake. RNA-sequencing analysis for gene expression indicates that the inflammatory pathway, lipid metabolism pathway, drug metabolism-cytochrome P450 pathway, cholesterol/bile acid metabolism pathway, and copper ion transport/metabolism pathway are compromised in the liver by two sizes of BSA@Cu2-xS NPs, while only SNPs show a complete recovery of altered gene expression after NPs discontinuation. This study demonstrates that the translational feasibility of small-sized BSA@Cu2-xS NPs as excellent nanoagents with manageable hepatotoxicity.

Study of female pelvic floor muscle in overactive bladder based on MRI 3D reconstruction.

BACKGROUND: This study examined the three-dimensional (3D) morphological changes of the urination and urinary continence anatomical structures in overactive bladder (OAB) patients, to offer a morphological data for OAB diagnosis and treatment. METHODS: Eleven OAB patients, 9 healthy females and 22 pelvic organ prolapse (POP) patients were enrolled and underwent MRI scans. The anatomical components of urination (bladder detrusor) and the urinary continence (main part of the urethral sphincter, compressor urethrae, and levator ani muscle (LAM) were 3D reconstructed and measured with Amira software. We also analyze the relativity between pelvic floor muscle's morphological parameters among the volunteers, OAB and POP group. RESULTS: Through 3D reconstruction, increased thickness and volume of the bladder detrusor were found in the OAB patients compared with volunteers (3.1 ± 0.7 mm vs. 1.9 ± 0.3 mm; P = 0.000 and 50,632.0 ± 19,724.7 mm3 vs. 23,386.6 ± 7826.3 mm3; P = 0.001). The volume of LAM showed no significant difference between the OAB patients and volunteers (27,089.4 ± 5015.0 mm3 vs. 27,294.4 ± 4461.4 mm3; P = 0.924); whereas, LAM's volume of the POP patients was significantly larger than that of the volunteers (34,130.6 ± 7968.3 mm3 vs. 27,294.4 ± 4461.4 mm3; P = 0.023). The thickness and volume of the main part of urethral sphincter were significantly lower in the OAB patients compared with volunteers (2.2 ± 0.5 mm vs. 2.7 ± 0.3 mm; P = 0.018 and 2558.6 ± 703.2 mm3 vs. 23,267.3 ± 681.9 mm3; P = 0.035). The volume of the compressor urethrae was significantly lower in the OAB patients than that in the volunteers (630.3 ± 301.2 mm3 vs. 866.1 ± 514.2 mm3; P = 0.247). CONCLUSIONS: In OAB patients, the bladder detrusor has long-term tension and contraction, which thickened muscle and increased volume, and aggravate urination. The compressor urethral and main part of urethral sphincter are weaker and the anterior part of LAM hiatus is relaxed, easily resulting in leakage of urine and ultimately incontinence. The MRI 3D reconstruction and measurement can help to evaluate pelvic floor urination and continence function, and accurately diagnose.

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.

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.

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.

[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.

[Yun's modified pelvic floor exercise improves female sexual dysfunction].

Objective: To study the effect and safety of Yun's modified pelvic floor exercise (PFE) in the treatment of female sexual dysfunction (FSD). METHODS: We enrolled 80 FSD patients from the Outpatient Department of Shanghai Fifth People's Hospital from August 2018 to January 2021 and randomized them into an experimental (n = 40) and a control group (n = 40), the former treated by Yun's modified PFE and the latter by traditional PFE, both for 8 weeks. After 0, 4 and 8 weeks of treatment, we evaluated the clinical effect by comparing the female sexual function indexes (FSFI), including sexual desire, sexual arousal, vaginal lubrication, orgasm, sexual satisfaction and sexual intercourse pain, the male partners' sexual satisfaction, and the pelvic floor muscle strength between the two groups of patients. RESULTS: Thirty-four of the patients in the experimental group and 36 in the control completed the treatment. There were no statistically significant differences in the baseline data between the two groups (P > 0.05). The FSFIs were significantly improved in both the experimental and control groups after 4 and 8 weeks of treatment compared with the baseline (P < 0.05), even more significantly in the experimental than in the control group at 8 weeks (P < 0.05). The effectiveness rate was remarkably increased from 52.8% at 4 weeks to 72.2% at 8 weeks in the experimental group (P < 0.05) and from 29.4% to 44.1% in the control (P < 0.05), even more significantly in the former than in the latter group (P < 0.05). Statistically significant differences were found in muscle tone and type I muscle strength between the two groups at 8 weeks (P < 0.05) but not at 4 weeks (P > 0.05). Type II muscle strength and partners' satisfaction were markedly higher in the experimental than in the control group at 4 and 8 weeks (P < 0.05). No adverse events were observed in either of the two groups. CONCLUSIONS: Yun's modified pelvic floor exercise can improve the symptoms of female sexual dysfunction, more effective than the traditional pelvic floor muscle exercise, and with no serious adverse reactions.

[Clinical effect of a scrotal rapid recovery dressing device in the treatment of acute epididymitis].

OBJECTIVE: To study the protective effect of a scrotal rapid recovery dressing device, scrotal girdle, on the scrotum of the patient with acute epididymitis, so as to improve the prognosis and the patient's satisfaction. METHODS: A total of 120 patients with acute epididymitis were treated in our hospital from December 2018 to November 2019, 60 with the scrotal girdle plus local cold compress in addition to antibiotics administration (the scrotal girdle group) and the other 60 with antibiotics only (the control group), all for 6 days. Then, comparisons were made between the two groups of patients in the improvement of scrotal swelling, total effectiveness rate and the patients' satisfaction with therapeutic outcomes. RESULTS: After 6 days of treatment, the patients in the scrotal girdle group, compared with the controls, showed significantly lower scrotal swelling scores (1.01 ± 0.34 vs 1.38 ± 0.20, P < 0.05), a higher total effectiveness rate (83.33% vs 65%, P < 0.05) and higher satisfaction with the therapeutic outcomes (86.67% vs 56.67%, P < 0.05). CONCLUSIONS: For the treatment of acute epididymitis, the application of the scrotal girdle for protection can significantly relieve scrotal pain and discomfort, improve the therapeutic effect and patients' satisfaction, and enhance the patients' recovery and quality of life.

[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.

In Vivo Photoacoustic/Single-Photon Emission Computed Tomography Imaging for Dynamic Monitoring of Aggregation-Enhanced Photothermal Nanoagents.

Emerging nanomedical strategy is to construct a nanoagent that affords not only diagnostic and therapeutic functions but also imaging-guided treatment. It is crucial to understand the in vivo biological processes of nanoagents for improving theranostic function and biosafety. Herein, we report a multimodal photoacoustic/single-photon emission computed tomography (SPECT) imaging technique to dynamically monitor the in vivo behaviors of nanoagents. Near-infrared cypate-induced silk fibroin nanoassembly was chosen as the nanoagent object due to their promise in biocompatibility and aggregation-enhanced photothermal effect. This unique effect makes the nanoagents useful for the integration of photoacoustic imaging and photothermal therapy. Moreover, the nanoagents are also labeled with the radionuclides (99mTc) to render SPECT imaging. Multimodal photoacoustic/SPECT imaging provides real time, noninvasive, sensitive, and whole-body 3D information about nanoagents' distribution in vivo. These results highlight the significance of visualizing the in vivo behaviors of nanoagents and locating the tumor in vivo, substantially benefiting the better treatment planning.

[Yun's optimized pelvic floor training therapy for idiopathic moderate overactive bladder with sexual dysfunction in young and middle-aged women].

OBJECTIVE: To explore the efficacy and safety of Yun's optimized pelvic floor training (OPFT) therapy for idiopathic moderate overactive bladder (OAB) with female sexual dysfunction (FSD) in young and middle-aged women. METHODS: Eighty 25－45 years old women with idiopathic moderate OAB companied by FSD were randomized into an experimental and a control group of equal number, the former treated by 6 weeks of Yun's OPFT therapy, followed by a 2-week washout period and then another 6 weeks of traditional pelvic floor muscle exercises (PFME), while the latter by 6 weeks of traditional PFME, followed by a 2-week washout period also and then another 6 weeks of Yun's OPFT. At 0, 6 and 14 weeks, we recorded the scores on overactive bladder symptoms (OABS), patient perception of bladder condition (PPBC), Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire-7 (IIQ-7), pelvic floor muscle strength, voided volume (VV), average urinary flow rate (Qavg), maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR), female sexual function index (FSFI), sexual satisfaction of the male partners and adverse events, and compared the parameters obtained between the two groups of patients. RESULTS: Thirty-eight of the patients in the experimental group and 29 controls completed the experiment. There were no statistically significant differences in the baseline data between the two groups (P > 0.05). After 6 and 14 weeks of treatment, the effectiveness rate was decreased from 71% to 58% in the experimental group, but increased from 45% to 72% in the control. Significant improvement was achieved in the experimental group in the OABS, PPBC, UDI-6 and IIQ-7 scores, pelvic floor muscle strength, VV, Qavg, Qmax, FSFI and sexual satisfaction of the male partners at 6 weeks as compared with the baseline (P < 0.05), and even more significant at 14 weeks than at 6 (P < 0.05), and so was it in the control group in the PPBC and IIQ-7 scores, VV, Qmax and sexual satisfaction of the male partners at 6 weeks (P < 0.05), and more significant in the OABS, PPBC, UDI-6 and IIQ-7 scores, pelvic floor muscle strength, FSFI and sexual satisfaction of the male partners at 14 than at 6 weeks (P < 0.05). The patients of the experimental group showed remarkably more improvement than the controls in the OABS, PPBC, UDI-6 and IIQ-7 scores, pelvic floor muscle strength, FSFI and sexual satisfaction of the male partners at 6 weeks (P < 0.05), while the control group exhibited significantly better improved OABS, PPBC, UDI-6 and IIQ-7 scores, pelvic floor muscle strength, VV, Qmax, PVR and FSFI than the experimental group at 14 weeks (P < 0.05). No serious adverse reactions were observed during the treatment. CONCLUSIONS: Yun's OPFT therapy can improve the symptoms of moderate OAB with FSD in young and middle-aged women, with significantly better effects than traditional pelvic floor muscle exercises.

Noninvasive Multimodal Imaging of Osteosarcoma and Lymph Nodes Using a 99mTc-Labeled Biomineralization Nanoprobe.

The accurate imaging of the lymph nodes represents a critical indicator for tumor staging and surgical planning (e.g., osteosarcoma). Clinically, nodal tracing using a radio-nanocolloid is often limited by the inaccessibility of real-time images and inadequate anatomical information. Herein, we present a 99mTc-labeled biomineralization nanoprobe for the advanced detection of osteosarcoma and lymph nodes with multimodal imaging. Through the exploitation of the complementary strengths of MRI/SPECT/NIR fluorescence, the fabricated nanoprobe exhibited suitable stability and biocompatibility characteristics and was shown to be able to be located in osteosarcoma. The lymphatic drainage and network in healthy mice were imaged in real-time using NIR fluorescence and SPECT/CT. Furthermore, we demonstrated that our 99mTc-biomineralization nanoprobe could be used for the high-resolution and high-sensitivity imaging analysis of lymphatic drainage in an orthotopic osteosarcoma model. Overall, the 99mTc-labeled biomineralization nanoprobe features promising characteristics to be used as an intraoperative visualization tool to aid in precise tumor imaging and nodal resection.

Detection of nanocarrier potentiation on drug induced phospholipidosis in cultured cells and primary hepatocyte spheroids by high content imaging and analysis.

Considerable effort has been made to develop nanocarriers for controlled drug delivery over the last decade, while it remains unclear how the strength of adverse drug effect will be altered when a drug is loaded on the nanocarrier. Drug-induced phospholipidosis (DIP) is characterized with excessive accumulation of phospholipids in cells and is common for cationic amphiphilic drugs (CAD). Previously, we have reported that PEGylated graphene oxide (PEG-GO) loaded with several CAD can potentiate DIP. In current study, we extended our study on newly identified phospholipidosis (PLD) inducers that had been identified from the Library of Pharmacologically Active Compounds (LOPAC), to investigate if PEO-GO loaded with these CAD can alter DIP. Twenty-two CAD were respectively loaded on PEG-GO and incubated with RAW264.7, a macrophage cell line. The results showed that when a CAD was loaded on PEG-GO, its strength of PLD induction can be enhanced, unchanged or attenuated. PEG-GO loaded with Ifenprodil exhibited the highest PEG-GO potentiation effect compared to Ifenprodil treatment alone in RAW264.7 cells, and this effect was confirmed in human hepatocellular carcinoma HepG2, another cell line model for PLD induction. Primary hepatocyte culture and spheroids mimicking in vivo conditions were used to further validate nanocarrier potentiation on DIP by Ifenprodil. Stronger phospholipid accumulation was found in PEG-GO/Ifenprodil treated hepatocytes or spheroids than Ifenprodil treatment alone. Therefore, evidences were provided by us that nanocarriers may increase the adverse drug effects and guidance by regulatory agencies need to be drafted for the safe use of nanotechnology in drug delivery.

Exposure and nephrotoxicity concern of bismuth with the occurrence of autophagy.

Metal nanoparticles or metal-based compounds have drawn attention in various fields ranging from industry to medicine because of their unique physicochemical properties. Bismuth (Bi) compounds and nanomaterials have been commonly used in alloys, electronic industry, batteries, and as flame retardants as well as for anti- Helicobacter pylori therapy, while the nanomaterial form has great potential for computed tomography imaging and thermotherapy, both of which will be introduced in this review. Although Bi was used for several decades, there is a lack of detailed information concerning their toxicity and mechanisms on human health. We described the toxicity of Bi on the kidney that seemed to be relatively known by researchers, while the mechanisms remain unclear. Recently, our group has found that Bi compounds, including bismuth nitrate (BN) and Bi nanomaterials, can induce autophagy in kidney cells. We also extended our findings by selecting five Bi compounds, and the results showed that BN, bismuth oxychloride, bismuth citrate, colloidal bismuth subcitrate, and Bi nanomaterials all induced slight cytotoxicity accompanied with autophagy. Although the role of autophagy in Bi-induced cytotoxicity and kidney injury is under investigation by us, autophagy may help with the exploration of the mechanisms of nephrotoxicity by Bi.