FBXO45 Knockdown Restrains the Progression of Bladder Cancer via the ERK/Cyclin D1/CDK4 Pathway.

BACKGROUNDS: F-box protein 45 (FBXO45) has been implicated in the progression of several diseases. Whether FBXO45 is involved in the development of bladder cancer remains unclear. Thus, this study focused on the effect of FBXO45 on the malignant progression of bladder cancer cells. METHODS: FBXO45 small-interference fragment was transfected into RT4 and 5637 cells by liposome-mediated transfection, and the knockdown efficiency of FBXO45 was verified by Western blot assay. The growth rate between FBXO45 knockdown cell lines and control cell lines was compared by counting kit 8 and plate cloning experiments. The motility of bladder cancer cells was observed via the Transwell test and Wound healing test. The effects of FBXO45 silencing on apoptosis and cell division were confirmed by flow cytometry. Western blot assay was performed to determine the function of FBXO45 knockdown on key proteins of cell apoptosis and the ERK/Cyclin D1/CDK4 pathway. RESULTS: After FBXO45 knockdown, the proliferation of bladder cancer cells was blocked (p < 0.01), and the migration and invasion abilities were reduced (p < 0.01). FBXO45 knockdown reduced the number of S-phase cells (RT4, p < 0.01; 5637, p < 0.05) and enhanced the apoptotic rate (p < 0.01). FBXO45 knockdown decreased the levels of p-ERK1/2, CDK4 and Cyclin D1 (p < 0.01). CONCLUSIONS: This study revealed that FBXO45 plays a carcinogenic role in bladder cancer via the ERK/Cyclin D1/CDK4 pathway, which provides a reference for the clinical treatment of patients with bladder cancer.

The reproducibility and predictivity of radiomic features extracted from dynamic contrast-enhanced computed tomography of hepatocellular carcinoma.

PURPOSE: To assess the reproducibility of radiomic features (RFs) extracted from dynamic contrast-enhanced computed tomography (DCE-CT) scans of patients diagnosed with hepatocellular carcinoma (HCC) with regards to inter-observer variability and acquisition timing after contrast injection. The predictive ability of reproducible RFs for differentiating between the degrees of HCC differentiation is also investigated. METHODS: We analyzed a set of DCE-CT scans of 39 patients diagnosed with HCC. Two radiologists independently segmented the scans, and RFs were extracted from each sequence of the DCE-CT scans. The same lesion was segmented across the DCE-CT sequences of each patient's scan. From each lesion, 127 commonly used RFs were extracted. The reproducibility of RFs was assessed with regard to (i) inter-observer variability, by evaluating the reproducibility of RFs between the two radiologists; and (ii) timing of acquisition following contrast injection (inter- and intra-imaging phase). The reproducibility of RFs was assessed using the concordance correlation coefficient (CCC), with a cut-off value of 0.90. Reproducible RFs were used for building XGBoost classification models for the differentiation of HCC differentiation. RESULTS: Inter-observer analyses across the different contrast-enhancement phases showed that the number of reproducible RFs was 29 (22.8%), 52 (40.9%), and 36 (28.3%) for the non-contrast enhanced, late arterial, and portal venous phases, respectively. Intra- and inter-sequence analyses revealed that the number of reproducible RFs ranged between 1 (0.8%) and 47 (37%), inversely related with time interval between the sequences. XGBoost algorithms built using reproducible RFs in each phase were found to be high predictive ability of the degree of HCC tumor differentiation. CONCLUSIONS: The reproducibility of many RFs was significantly impacted by inter-observer variability, and a larger number of RFs were impacted by the difference in the time of acquisition after contrast injection. Our findings highlight the need for quality assessment to ensure that scans are analyzed in the same physiologic imaging phase in quantitative imaging studies, or that phase-wide reproducible RFs are selected. Overall, the study emphasizes the importance of reproducibility and quality control when using RFs as biomarkers for clinical applications.

Peripheral Coagulation Parameters and Prostate Cancer Association: A Retrospective Study and Mendelian Randomization.

Background: The limitations of prostate-specific antigen (PSA) in diagnosing prostate cancer (PCa) necessitate the exploration of novel biomarkers. Recent studies suggest a potential link between coagulation markers, particularly fibrinogen and D-dimer, and PCa. Methods: A retrospective single-center analysis on 466 biopsy-undergone patients was conducted, categorized into PCa and benign prostatic hyperplasia (BPH) groups. Baseline and coagulation parameter levels were analyzed. Utilizing a Mendelian randomization (MR) approach, we investigated the causative relationship between D-dimer and PCa risk. Results: Individuals with PCa, compared with those with BPH, exhibited significantly higher D-dimer levels (P < .001), total PSA (P < .001), and PSA density (P < .001). Fibrinogen levels did not exhibit significant differences (P = .505). The MR analysis suggested a probable causal link between elevated D-dimer levels and an increased risk of PCa (odds ratio: 1.81, 95% confidence interval: 1.48-2.21, P = 7.4 × 10-9). Conclusions: This research highlights D-dimer as a potential biomarker for diagnosing PCa, supported by clinical and MR analyses. The study paves the way for future large-scale, multi-center research to corroborate these findings and further explore the relationship between coagulation markers and PCa mechanisms.

Relationship between workplace violence, job satisfaction, and burnout among healthcare workers in mobile cabin hospitals in China: Effects of perceived stress and work environment.

Background: Although workplace violence is prevalent in the healthcare system, the relationship between workplace violence, job satisfaction, and burnout among healthcare workers (HCWs) in mobile cabin hospitals in China during the COVID-19 pandemic has not yet been investigated. This study analyzes the mediating effects of perceived stress and work environment in the relationship between workplace violence, job satisfaction, and burnout. Methods: A cross-sectional study was conducted in December 2022 on 1,199 frontline HCWs working in mobile cabin hospitals in Chongqing, China, during the COVID-19 pandemic. Multiple linear regression and mediation analysis were performed. Results: A positive correlation was observed between workplace violence and burnout (r = 0.420, P < 0.01) and perceived stress (r = 0.524, P < 0.01), and a negative correlation was observed with job satisfaction (r = -0.254, P < 0.01). The perceived stress was positively correlated with burnout (r = 0.528, P < 0.01) and negatively with job satisfaction (r = -0.397, P < 0.01). Job satisfaction was negatively correlated with burnout (r = -0.300, P < 0.01). Perceived stress plays a significant mediating role between workplace violence and job burnout and between workplace violence and job satisfaction. The work environment has a significant moderating effect between workplace violence and job burnout and between workplace violence and job satisfaction. Conclusion: To reduce burnout among HCWs, hospital administrators should focus on reducing the incidence of workplace violence and perceived stress from work and on improving the work environment and job satisfaction.

Machine learning-based identification of contrast-enhancement phase of computed tomography scans.

Contrast-enhanced computed tomography scans (CECT) are routinely used in the evaluation of different clinical scenarios, including the detection and characterization of hepatocellular carcinoma (HCC). Quantitative medical image analysis has been an exponentially growing scientific field. A number of studies reported on the effects of variations in the contrast enhancement phase on the reproducibility of quantitative imaging features extracted from CT scans. The identification and labeling of phase enhancement is a time-consuming task, with a current need for an accurate automated labeling algorithm to identify the enhancement phase of CT scans. In this study, we investigated the ability of machine learning algorithms to label the phases in a dataset of 59 HCC patients scanned with a dynamic contrast-enhanced CT protocol. The ground truth labels were provided by expert radiologists. Regions of interest were defined within the aorta, the portal vein, and the liver. Mean density values were extracted from those regions of interest and used for machine learning modeling. Models were evaluated using accuracy, the area under the curve (AUC), and Matthew's correlation coefficient (MCC). We tested the algorithms on an external dataset (76 patients). Our results indicate that several supervised learning algorithms (logistic regression, random forest, etc.) performed similarly, and our developed algorithms can accurately classify the phase of contrast enhancement.

First report of Botryosphaeria dothidea causing fruit rot on Chinese olive (Canarium album Raeusch.) in Guangdong province of China.

Chinese olive (Canarium album Raeusch.) is a traditional Chinese medicinal plant, mainly cultivated in Guangdong and Fujian provinces in China (Lai et al. 2022). In October 2023, Chinese olive fruit spots were observed in all the Chinese olive orchards surveyed in Chaozhou city (23.75°N, 116.67°E) of Guangdong, with an incidence up to 15%. Early disease symptoms on fruits appeared as circular or irregular, dark brown to black spots with yellowish lesions, and later the spots slowly coalesced to form large necrotic areas, which seriously affected the fruit marketability. To isolate the causal agent, small pieces (~0.3 mm2) of fruit tissue were excised from the lesion margins, and surface-disinfested with 75% (v/v) ethanol for 1 min, followed by 1% NaClO for 3 min, and rinsed three times with sterile water. The pieces were then placed on potato-dextrose-agar (PDA) and incubated at 27°C. Ultimately, four fungal isolates were obtained with similar morphology phenotypes, colonies initially appeared white with irregular margins and after 4-6 days turned dark gray gradually with dense aerial myceliu. Microscopy revealed conidia were single-celled, hyaline, aseptate, fusiform to subclavate, and measured 18.1-22.5 µm × 6.4-9.3 µm (19.8 × 7.4 m on average, n = 30), which were consistent with those descriptions of Botryosphaeria dothidea (Vasic et al. 2013; Zhang et al. 2023). To further identity the isolates, partial sequences of ribosomal transcribed spacer (ITS), translation elongation factor 1-α (TEF1-α), and ß-tubulin (TUB2) genes were amplified using primers ITS1/ITS5, TEF-F/R, TUB2-F/R, respectively (Xu et al., 2023; Hong et al. 2006). The sequences of four isolates were identical, and those of representative strain GDCZ-1 were deposited in GenBank (ITS, OR584295; TEF1-α, OR685157; TUB2, OR685158). Using Neighbor-Joining algorithm, phylogenetic tree based on concatenated sequences of ITS, TEF1-α, and TUB2 showed that GDCZ-1 clustered with B. dothidea. To fulfill Koch's postulates, pathogenicity tests were performed on healthy Chinese olive fruits using the needle-prick inoculation method. The fruits were wounded with a sterile needle at the equatorial area (depth of 3-4 mm), and inoculated with 10 µL of spore suspension (106 /mL). The control fruits were inoculated with sterile water. Inoculated fruits were placed in sterile plastic containers to maintain high relative humidity (almost 100%) and incubated at 27°C. After 4 days, the inoculated fruits showed similar symptoms with those observed in the field infected fruits, while the control remained asymptomatic. Pathogen re-isolated from the inoculated fruits showed identical morphological characteristics to the original isolate GDCZ-1. As far as we know, fruit rot caused by Alternaria alternata has been recently reported on C. album in China (Shao et al. 2024). To our knowledge, this is the first report of B. dothidea causing fruit rot disease on C. album in Guangdong. Our report will provide crucial information for studying the epidemiology and management of this disease.

Comparative physiological and transcriptome analysis provide insights into the inhibitory effect of osthole on Penicillium choerospondiatis.

Blue mold induced by Penicillium choerospondiatis is a primary cause of growth and postharvest losses in the fruit of Phyllanthus emblica. There is an urgent need to explore novel and safe fungicides to control this disease. Here, we demonstrated osthole, a natural coumarin compound isolated from Cnidium monnieri, exhibited a strong inhibitory effect on mycelia growth, conidial germination rate and germ tube length of P. choerospondiatis, and effectively suppressed the blue mold development in postharvest fruit of P. emblica. The median effective concentration of osthole was 9.86 mg/L. Osthole treatment resulted in cellular structural disruption, reactive oxygen species (ROS) accumulation, and induced autophagic vacuoles containing cytoplasmic components in fungal cells. Transcriptome analysis revealed that osthole treatment led to the differentially expressed genes mainly enriched in the cell wall synthesis, TCA cycle, glycolysis/ gluconeogenesis, oxidative phosphorylation. Moreover, osthole treatment led to increase genes expression involved in peroxisome, autophagy and endocytosis. Particularly, the autophagy pathway related genes (PcATG1, PcATG3, PcATG15, PcATG27, PcYPT7 and PcSEC18) were prominently up-regulated by osthole. Summarily, these results revealed the potential antifungal mechanism of osthole against P. choerospondiatis. Osthole has potentials to develop as a natural antifungal agent for controlling blue mold disease in postharvest fruits.

The efficacy of peritoneal flap fixation on symptomatic lymphocele formation following robotic-assisted laparoscopic radical prostatectomy with pelvic lymph node dissection: a systematic review and meta-analysis.

BACKGROUND: Pelvic lymphocele is the most common complication after robot-assisted radical prostatectomy (RARP) with pelvic lymph node dissection (PLND), of which symptomatic lymphocele (sLC) ranges up to 10% and is associated with poorer perioperative outcomes. Peritoneal flap fixation (PFF) is a promising intraoperative modification to reduce sLC formation but the clinical evidence failed to reach consistency. MATERIALS AND METHODS: Randomized and nonrandomized comparative studies comparing postoperative sLC occurrence with or without PFF after RARP with PLND were identified through a systematic literature search via MEDLINE/PubMed, Embase, Web of Science, and CENTRAL up to July 2023. Outcome data of sLC occurrence (primary) and major perioperative events (secondary) were extracted. Mean difference and risk ratio with 95% CI were synthesized as appropriate for each outcome to determine the cumulative effect size. RESULTS: Five RCTs and five observatory studies involving 3177 patients were finally included in the qualitative and quantitative analysis. PFF implementation significantly reduced the occurrence of sLC (RR 0.35, 95% CI: 0.24-0.50), and the specific lymphocele-related symptoms, without compromised perioperative outcomes including blood loss, operative time, and major nonlymphocele complications. The strength of the evidence was enhanced by the low risk of bias and low inter-study heterogeneity of the eligible RCTs. CONCLUSION: PFF warrants routine implementation after RARP with PLND to prevent or reduce postoperative sLC formation.

Analysis of factors associated with delayed diagnosis and treatment of testicular torsion in 1005 cases from Chongqing city, China: a cross-sectional study.

This study aimed to investigate the clinical and social factors of delayed treatment for testicular torsion (TT) and to explore the risk factors of testicular excision in China. The clinical data of 1005 patients with TT who were admitted to 48 medical institutions in Chongqing city (China) from January 2012 to December 2021 were retrospectively analyzed. It was revealed that the misdiagnosis rates of non-senior (junior and middle) grade doctors and senior doctors were 25.1% and 9.6%, respectively. The proportion of TT patients who received timely treatment (within 6 h after onset of symptoms) was 23.8%. The results of the multivariable logistic regression analysis indicated that absent cremasteric reflex was a protective factor for delayed surgery of more than 6 h from onset of symptoms to surgery. Misdiagnosis, consultation with a non-urologist as the first consultant doctor, absence blood flow in color Doppler ultrasound, negative high-riding testis findings, the presence of fever, and non-manual detorsion were identified as risk factors associated with delayed surgery (more than 6 h from the onset of symptoms) for TT. Furthermore, misdiagnosis, non-urologist first-consultant doctor, absent blood flow in DUS, non-manual detorsion, fever, degree of cord twisting > 180, and the initial diagnosis in tertiary hospitals were risk factors for orchidectomy. Having TT on the right side, and the presence of nausea and vomiting were identified as protective factors for orchidectomy. Technical training in the diagnosis and treatment of TT should be extended to primary hospitals and doctors to significantly improve their accuracy in managing this condition.

Construction and evaluation of a novel prognostic risk model of aging-related genes in bladder cancer.

Background: Bladder cancer (BLCA) is the most common malignancy of the urinary system. Muscle-invasive bladder cancer (MIBC), which constitutes approximately 25% of all BLCA cases, is characterized by frequent recurrence and early onset of metastasis. Bladder cancer most commonly occurs in elderly patients and is significantly associated with aging. However, the prognostic value of age-related genes in BLCA, especially in MIBC, remains unclear. Materials and methods: Training and testing sets were obtained from The Cancer Genome Atlas BLCA project. Differentially expressed genes between BLCA and normal samples intersected with human aging-related genes. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were used to identify prognostic aging-related signatures, followed by the construction of a risk score model and nomogram. Kaplan-Meier and receiver operating characteristic analyses were conducted to assess the predictive power. An independent BLCA cohort of 165 samples was included for external validation. The CIBERSORT algorithm was used to explore the characteristics of the immune microenvironment. Results: Seven genes (IGF1, NGF, GCLM, PYCR1, EFEMP1, APOC3, and IFNB1) were identified by Cox and least absolute shrinkage and selection operator analyses. After combining the gene signature with the clinical parameters of patients with BLCA, a risk-prognosis model and nomogram were constructed and validated with the testing set. Bladder cancer cases with high 7-gene signature scores (high-risk group) and low scores (low-risk group) showed distinct prognoses. Furthermore, 7 types of immune cells were significantly altered between the low- and high-risk groups. Conclusions: Collectively, our data provide a 7-gene signature that serves as a potential biomarker for BLCA, especially MIBC. Moreover, this 7-gene signature highlights the role of the tumor immune microenvironment in prognosis and thus might be related to the response to anti-programmed cell death protein 1-based immunotherapy.

High-performance towing cable hydrophone array with an improved ultra-sensitive fiber-optic distributed acoustic sensing system.

A high-performance towing cable hydrophone array based on an improved ultra-sensitive fiber-optic distributed acoustic sensing system (uDAS) with picostrain sensitivity is demonstrated and tested in sea trial, for the first time. A new composite transducer is designed and optimized to enhance the acoustic pressure sensitivity significantly. A sea trial is carried out to test the performances of such a hydrophone array, including flow noise, underwater acoustic signal capture capacity, beamforming processing and localization of artificial source targets. The array exhibits high sensitivity and low noise floor. An average sensitivity of -129.23 dB re rad/µPa at frequencies from 10 Hz to 1500 Hz has been achieved. The localization at distances of 5 km and 10 km is realized, respectively, validating the excellent remote detection and positioning capability of the hydrophone system. The proposed towing cable system, with high sensitivity, simple structure and remote target localization ability, may pave a way for development of the next generation of high-performance light-weighting hydrophone arrays for towing applications.

Relationship between rumination and post-traumatic growth in mobile cabin hospital nurses: The mediating role of psychological resilience.

Psychological resilience helps individuals to actively respond to various emergencies, but its mediating role between the rumination and post-traumatic growth (PTG) of nurses remains unknown. Our study aimed to explore the extent to which psychological resilience mediates the association between rumination and PTG among nurses working in mobile cabin hospitals. This cross-sectional survey was conducted on 449 medical team members working in mobile cabin hospitals to support the prevention and control of coronavirus disease 2019 in Shanghai, China in 2022. Pearson correlation analysis was applied to assess the correlation between rumination, psychological resilience, and PTG. Structural equation models were used to examine the mediating role of psychological resilience between rumination and PTG. Our study results showed that deliberate rumination directly promoted psychological resilience and PTG and had positive effects on PTG through the mediating effect of psychological resilience. Invasive rumination had no direct effect on PTG. However, it had a negative effect on PTG through the mediating effect of psychological resilience. Together the results of this study indicate that the mediating effect of psychological resilience was significant in the association of rumination and PTG among mobile cabin hospital nurses, with a higher individual psychological resilience level helping nurses to achieve PTG. Therefore, targeted interventions should be implemented to improve nurses' psychological resilience and guide their rapid growth.

Renal clear cancer cells regulate the differentiation of urine-derived stem cells to carcinoma-associated fibroblasts via RUNX3/TGF-ß1 signaling axis.

Clear cell renal cell carcinoma (ccRCC), the most common pathological subtype of renal cancer, is one of the significant health concerns due to limited clinically effective treatments. Nevertheless, targeting carcinoma-associated fibroblasts in the tumor microenvironment has emerged as a promising innovative strategy for renal cancer therapy. Thus, this study is aimed to explore the role and molecular mechanism of urine-derived stem cells (USCs) in the progression and metastasis of ccRCC. Initially, wound-healing and transwell experiments were used to assess the migration and invasion abilities of the cells. Then, western blot analysis (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were used to demonstrate the relevant protein and messenger RNA expression levels. Finally, hematoxylin-eosin and immunohistochemical stainings were performed to evaluate metastasis and protein expression in lung tumors. The coculture of USCs with the ccRCC cell lines significantly enhanced their migratory and invasive abilities. WB and qRT-PCR analyses exhibited that ccRCC cell lines significantly increased cell mobility markers transcriptional and protein levels in USCs. Finally, the in vivo investigations in nude mice showed that USCs promoted the proliferation and migration of ccRCC-based xenograft tumors. In summary, these findings demonstrated that USCs promoted ccRCC tumorigenesis and development in vivo and in vitro by regulating the Runt-related transcription factor 3/transforming growth factor-ß1 signaling axis.

Photoacoustic maximum amplitude projection microscopy by ultra-low data sampling.

Photoacoustic microscopy (PAM) has attracted increasing research interest in the biomedical field due to its unique merit of combining light and sound. In general, the bandwidth of a photoacoustic signal reaches up to tens or even hundreds of MHz, which requires a high-performance acquisition card to meet the high requirement of precision of sampling and control. For most depth-insensitive scenes, it is complex and costly to capture the photoacoustic maximum amplitude projection (MAP) images. Herein, we propose a simple and low-cost MAP-PAM system based on a custom-made peak holding circuit to obtain the extremum values by Hz data sampling. The dynamic range of the input signal is 0.01-2.5 V, and the -6-dB bandwidth of the input signal can be up to 45 MHz. Through in vitro and in vivo experiments, we have verified that the system has the same imaging ability as conventional PAM. Owing to its compact size and ultra-low price (approximately $18), it provides a new performance paradigm for PAM and opens up a new way for an optimal photoacoustic sensing and imaging device.

Upregulation of the ZNF148/PTX3 axis promotes malignant transformation of dendritic cells in glioma stem-like cells microenvironment.

BACKGROUND: The recent development of dendritic cell (DC)-based immunotherapy has resulted in advances in glioblastoma multiforme (GBM) treatment. However, the cell fate of DCs in the GBM microenvironment, especially in microenvironments in which glioma stem cell (GSCs)-mediated remodeling has resulted in highly immunosuppressive conditions, has not yet been fully investigated. METHODS: Observed the interaction between GSCs and primary cultured DCs in a dual-color tracing model, monoclonal and continuously passaged highly proliferative DCs, and named transformed DCs (t-DCs). The expression of DC-specific surface markers was analyzed using RT-PCR, chromosome karyotype, and flow cytometry. The expression of long pentraxin 3 (PTX3) and its transcription factor zinc finger protein 148 (ZNF148) in t-DCs was detected using qRT-PCR and western blot. CCK8 and transwell assays were conducted to assess the effect of ZNF148 and PTX3 on the proliferation, migration, and invasion of t-DCs. Bioinformatics analysis, dual-luciferase reporter assay, and chromatin immunoprecipitation (ChIP)-qPCR assay were used to explore the relation between ZNF148 and PTX3. RESULTS: Transformed DCs (t-DCs) still expressed DC-specific surface markers, namely, CD80 and CD11c, and immune-related costimulatory molecules, namely, CD80, CD86, CD40, and ICAM-1. However, the expression levels of these molecules in t-DCs decreased moderately compared to those in naive DCs. Stable overexpression of PTX3 further promoted the proliferation and migration of t-DCs in vitro, decreased the expression of costimulatory molecules, and increased the tumorigenicity of t-DCs in vivo. The transcription factor zinc finger protein 148 (ZNF148) was directly bound to the PTX3 promoter region and enhanced PTX3 expression. Downregulation of ZNF148 significantly decreased PTX3 expression and reduced the proliferation and migration of t-DCs. Overexpression of ZNF148 significantly increased PTX3 expression and promoted the proliferation and migration of t-DCs, achieving the same biological effects as PTX3 overexpression in t-DCs. Simultaneously, the downregulation of ZNF148 partially reversed the effect of PTX3 overexpression in t-DCs. CONCLUSION: The ZNF148/PTX3 axis played an important role in regulating the malignant transformation of DCs after cross-talk with GSCs, and this axis may serve as a new target for sensitizing GBM to DC-based immunotherapy.

Folate modified dual pH/reduction-responsive mixed micelles assembled using FA-PEG-PDEAEMA and PEG-SS-PCL for doxorubicin delivery.

Aiming at achieving the concurrent performances of high loading, well controlled release and active targeted delivery, folate (FA) modified dual pH/reduction-responsive mixed polymeric micelles were rationally assembled using FA-PEG-PDEAEMA and PEG-SS-PCL by dissipative particle dynamics (DPD) simulations. The optimized polymers PEG112-PDEAEMA40, FA-PEG112-PDEAEMA40, and PEG112-SS-PCL70 were synthesized and characterized using 1H NMR, FT-IR and GPC, and their mixed micelles were applied for doxorubicin (DOX) delivery. The drug loading capacity (LC) and encapsulation efficiency (EE) values of the MIX1 (FA-PEG112-PDEAEMA40/PEG112-SS-PCL70) at a DOX/polymer feeding ratio of 15 mg/30 mg were 20.22% and 50.69%, which were higher than those of single polymer micelles and MIX2 (PEG112-PDEAEMA40/PEG112-SS-PCL70). Particle size distributions, mesoscopic morphologies, DPD simulations and in vitro drug release profiles all confirmed the well-controlled release performance of the DOX-loaded micelles formed by MIX1: slow DOX release with a cumulative release of 20.46% in the neutral environment and accelerated release with a cumulative release of 74.20% at pH 5.0 + 10 mM DTT within 120 h, which were similar to those of MIX2. Cytotoxicity assay found that both MIX1 and MIX2 blank micelles were biocompatible, and a superior inhibitory effect of the FA-modified DOX-loaded micelles MIX1 on HepG2 cells was found compared to that of free DOX and non-FA-modified DOX-loaded micelles MIX2. All of these confirmed the superiority of MIX1 micelles with high loading capacity, well controlled release, and enhanced inhibitory effects on HepG2 cells, which might be a prospective candidate for anticancer drug delivery.

Preoperative α-blockade versus no blockade for pheochromocytoma-paraganglioma patients undergoing surgery: a systematic review and updated meta-analysis.

BACKGROUND: Surgical resection of pheochromocytomas and paragangliomas (PPGLs) is associated with a significant risk of intraoperative hemodynamic instability and cardiovascular complications. α-blockade remains the routine preoperative medical preparation despite controversies over the lack of evidence. We presented an updated meta-analysis to ulteriorly evaluate the potential efficacy of preoperative α-blockade versus no blockade for PPGL patients undergoing surgery. MATERIALS AND METHODS: Randomized and nonrandomized comparative studies assessing preoperative α-blockade for PPGL surgery in adults were identified through a systematic literature search via MEDLINE, Embase, Web of Science, and CENTRAL up to November 2022. Outcome data of intraoperative hemodynamic parameters and major postoperative events were extracted. Mean difference and risk ratio were synthesized as appropriate for each outcome to determine the cumulative effect size. RESULTS: Fifteen nonrandomized studies involving 3542 patients were finally eligible. Intraoperatively, none of the analyzed hemodynamic parameters differed between patients with or without α-blockade: maximum and minimum systolic blood pressure, hypertensive and hypotensive hemodynamic instability episodes, and peak heart rate, subgroup analysis of normotensive PPGL patients yielded similar results with the overall effects. Postoperatively, α-blockade was associated with prolonged hypotension and vasopressor usage (risk ratio: 4.21, 95% CI: 1.17-15.18, P =0.03). ICU admission, length of stay, overall cardiovascular morbidity, and mortality were similar between the two groups. CONCLUSIONS: Preoperative α-blockade ensured neither more stable intraoperative hemodynamics nor better perioperative outcome over no blockade for PPGL surgery. However, large-volume randomized controlled trials are still warranted to ascertain these findings.

Case report: Sarcomatoid urothelial carcinoma of the renal pelvis masquerading as a renal abscess.

Sarcomatoid urothelial carcinoma (SUC), a rare tumor of the urinary tract epithelium, exhibits a high degree of malignancy and therefore a poor prognosis. Due to the absence of specific clinical presentations and imaging findings, SUC of the renal pelvis masquerades as a renal abscess is frequently under-recognized or misdiagnosed as benign inflammatory disease, resulting in delayed or erroneous treatment. Here, we report a patient with SUC of the renal pelvis who presented with a renal abscess. Repeated anti-inflammatory treatment was ineffective. Unexpectedly, cancerous cells were detected in subsequent exfoliative cytology of nephrostomy drainage fluid. In accordance with this, radical surgery and postoperative chemotherapy were conducted. Fortunately, neither recurrence nor metastasis occurred during a one-year follow-up.

Systematic Design and Study of Star-like Polymeric Prodrug Unimolecular Micelles ß-CD-P[CL-co-(ACL-g-DOX)-SS-MPEG]21 by DPD Simulations.

Unimolecular micelles composed of a single polymeric molecule have recently attracted significant attention in anti-cancer drug delivery due to their high thermodynamic stability and small particle sizes. Applying the prodrug strategy to unimolecular micelles may provide superior nano-drug carriers with simultaneous high stability, low drug leakage, and well-drug loading capacity. However, the formation mechanism of the unimolecular prodrug micelles, the superiority of the prodrug strategy, as well as the prodrug controlled release mechanism were scantily understood at the mesoscopic scale. In this work, dissipative particle dynamics mesoscopic simulations were employed to investigate the self-assembly behavior, formation conditions, drug distribution regularities, and the prodrug release process of the star-like polymeric prodrug unimolecular micelles formed by ß-CD-P[CL-co-(ACL-g-DOX)-SS-MPEG]21. A special bond-breaking script was used to accomplish the bond-breaking simulation of the grafted DOX bonds and the disulfide bonds. Results showed that to form well monodispersed and superior DOX-loaded unimolecular micelles, the polymer concentration should be well controlled at low volume fractions (≤10.59%), and the detailed molecular structure of the polymer was suggested as ß-cyclodextrin-P[caprolactone-co-(amino caprolactone-g-doxorubicin)-disulfide-methyl polyethylene glycol]21) (ß-CD-P[CL30-co-(ACL-g-DOX)8-SS-MPEG49]21). By comparison with the DOX physically loaded micelles, it was found that the prodrug unimolecular micelles with DOX grafted on the polymer displayed no drug leakage and superior drug loading capacity. Simulations on the prodrug release process showed that the prodrug unimolecular micelles assembled by ß-CD-P[CL30-co-(ACL-g-DOX)8-SS-MPEG49]21 would provide good dual pH/reduction-responsive DOX release performance.

Efficacy of Shuganjieyu capsule for treatment of neurologic disorders combined with depression: A meta-analysis.

Shuganjieyu capsule (SGJY) is the first Chinese herbal medicine approved for treatment of depression; however, the Shuganjieyu capsule efficacy in patients with neurologic disorders combined with depression remains to be determined. Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI) and other electronic databases were searched to obtain relevant studies through May 2019. Newcastle-Ottawa and Jadad scales are used for the quality assessed. Sensitivity analysis, subgroup analysis and meta-regression were performed to evaluate sources of heterogeneity. Sixty-seven studies were selected for further analysis. Patients who had Shuganjieyu therapy had a higher effective rate and lower Hamilton Depression Rating Scale (HAM-D) score compared to patients who had non-shuganjieyu therapy. In addition, Shuganjieyu capsule improve symptoms of patients with stroke (National Institutes of Health Stroke Scale (NIHSS) score: Weighted mean difference (WMD)= -2.64; 95% CI: -3.95 to -1.33; P<0.001), Parkinson's disease score: WMD= -2.53; 95% CI: -3.92 to -1.14; P<0.001), and sleep disorders (Pittsburgh Sleep Quality Index (PSQI) score: WMD= -4.97; 95% CI: -7.56 to -2.38; P<0.001). Our results demonstrated that there were clinical benefits for patients with neurologic disorders after Shuganjieyu capsule therapy compared with non-shuganjieyu therapy with respect to effective rate and HAM-D, NIHSS, UPDRS and PSQI scores.