Identification of novel protein biomarkers from the blood and urine for the early diagnosis of bladder cancer via proximity extension analysis.

BACKGROUND: Bladder cancer (BC) is a very common urinary tract malignancy that has a high incidence and lethality. In this study, we identified BC biomarkers and described a new noninvasive detection method using serum and urine samples for the early detection of BC. METHODS: Serum and urine samples were retrospectively collected from patients with BC (n = 99) and healthy controls (HC) (n = 50), and the expression levels of 92 inflammation-related proteins were examined via the proximity extension analysis (PEA) technique. Differential protein expression was then evaluated by univariate analysis (p < 0.05). The expression of the selected potential marker was further verified in BC and adjacent tissues by immunohistochemistry (IHC) and single-cell sequencing. A model was constructed to differentiate BC from HC by LASSO regression and compared to the detection capability of FISH. RESULTS: The univariate analysis revealed significant differences in the expression levels of 40 proteins in the serum (p < 0.05) and 17 proteins in the urine (p < 0.05) between BC patients and HC. Six proteins (AREG, RET, WFDC2, FGFBP1, ESM-1, and PVRL4) were selected as potential BC biomarkers, and their expression was evaluated at the protein and transcriptome levels by IHC and single-cell sequencing, respectively. A diagnostic model (a signature) consisting of 14 protein markers (11 in serum and three in urine) was also established using LASSO regression to distinguish between BC patients and HC (area under the curve = 0.91, PPV = 0.91, sensitivity = 0.87, and specificity = 0.82). Our model showed better diagnostic efficacy than FISH, especially for early-stage, small, and low-grade BC. CONCLUSION: Using the PEA method, we identified a panel of potential protein markers in the serum and urine of BC patients. These proteins are associated with the development of BC. A total of 14 of these proteins can be used to detect early-stage, small, low-grade BC. Thus, these markers are promising for clinical translation to improve the prognosis of BC patients.

Prostate cancer-derived small extracellular vesicle proteins: the hope in diagnosis, prognosis, and therapeutics.

Current diagnostic tools for prostate cancer (PCa) diagnosis and risk stratification are insufficient. The hidden onset and poor efficacy of traditional therapies against metastatic PCa make this disease a heavy burden in global men's health. Prostate cancer-derived extracellular vesicles (PCDEVs) have garnered attention in recent years due to their important role in communications in tumor microenvironment. Recent advancements have demonstrated PCDEVs proteins play an important role in PCa invasion, progression, metastasis, therapeutic resistance, and immune escape. In this review, we briefly discuss the applications of sEV proteins in PCa diagnosis and prognosis in liquid biopsy, focus on the roles of the PCa-derived small EVs (sEVs) proteins in tumor microenvironment associated with cancer progression, and explore the therapeutic potential of sEV proteins applied for future metastatic PCa therapy.

Identification of novel biomarkers in Hunner's interstitial cystitis using the CIBERSORT, an algorithm based on machine learning.

BACKGROUND:  Hunner's interstitial cystitis (HIC) is a complex disorder characterized by pelvic pain, disrupted urine storage, and Hunner lesions seen on cystoscopy. There are few effective diagnostic biomarkers. In the present study, we used the novel machine learning tool CIBERSORT to measure immune cell subset infiltration and potential novel diagnostic biomarkers for HIC. METHODS: The GSE11783 and GSE57560 datasets were downloaded from the Gene Expression Omnibus for analysis. Ten HIC and six healthy samples from GSE11783 were analyzed using the CIBERSORT algorithm. Gene Set Enrichment Analysis (GSEA) was performed to identify biological processes that occur during HIC pathogenesis. Finally, expression levels of 11 T cell follicular helper cell (Tfh) markers were compared between three healthy individuals and four patients from GSE57560. RESULTS: Six types of immune cells in HIC from GSE11783 showed significant differences, including resting mast cells, CD4+ memory-activated T cells (CD3+ CD4+ HLA-DR+ cells), M0 and M2 macrophages, Tfh cells, and activated natural killer cells. Except for plasma cells, there were no significant differences between Hunner's lesion and non-Hunner's lesion areas in HIC. The GSEA revealed significantly altered biological processes, including antigen-antibody reactions, autoimmune diseases, and infections of viruses, bacteria, and parasites. There were 11 Tfh cell markers with elevated expression in patients from GSE57560. CONCLUSION: This was the first demonstration of Tfh cells and CD3+ CD4+ HLA-DR+ cells with elevated expression in HIC. These cells might serve as novel diagnostic biomarkers.

Safety and efficacy of en bloc transurethral resection versus conventional transurethral resection for primary nonmuscle-invasive bladder cancer: a meta-analysis.

BACKGROUND: The purpose of this meta-analysis is to compare the safety and efficacy of en bloc transurethral resection of bladder tumor (EBRT) versus conventional transurethral resection of bladder tumor (CTURBT). METHODS: We performed a meta-analysis of relevant articles through November 2019 using PubMed, Embase, and Cochrane Central Register to compare the safety and efficacy of EBRT versus CTURBT. The main endpoint included the operation time (OT), hospitalization time (HT), catheterization time (AT), perioperative period complications, bladder detrusor muscle found in the specimen, the residual tumor on the base, the ratio of the same site recurrence, and 12/24/36-month recurrence rate. Cochrane Collaboration's Revman software, version 5.3, was used for statistical analysis. RESULTS: A total of 19 studies with 2651 patients were included, 1369 underwent EBRT and 1282 underwent CTURBT. Patients treated with EBRT had a significantly lower AT, HT, obturator nerve reflex, bladder perforation, bladder irritation, postoperative complications, and 24-month recurrence rate than those who underwent CTURBT. While no significant difference was found in terms of OT, the ratio of bladder detrusor muscle found in the specimen, the residual tumor on the base, 12-month recurrence rate, 36-month recurrence rate, and the ratio of the same site recurrence. In mitomycin subgroup, EBRT was superior to CTURBT in terms of 12/24-month recurrence rate. Similarly, in the prospective subgroup and retrospective subgroup, EBRT had a lower 24-month recurrence rate than CTURBT. However, no significant difference was found in the low, intermediate, and high-risk group in the light of 12-36-month recurrence rate. CONCLUSIONS: Based on the included 19 articles, EBRT had a significantly lower AT, HT, intraoperative and postoperative complications, and 24-month recurrence rate than those treated with CTURBT. Well-designed randomized controlled trials were needed to reevaluate these outcomes. TRIAL REGISTRATION: This meta-analysis was reported in agreement with the PRISMA statement and was registered on PROSPERO 2019 CRD42019121673.

Progress in applications of 18F-fluciclovine in diagnosis of prostate cancer. / 18F-fluciclovineåº”ç”¨äºŽå‰åˆ—è ºç™Œè¯Šæ–­çš„è¿›å±•.

Prostate cancer is the most common malignancy tumor among men in developed countries. The incidence rate in recent years is also increasing in China. With the development of technology, the application of PET/CT examination has been augmented in the diagnosis of prostate cancer. In order to detect prostate cancer more safely and effectively, new types of targeted tracer for PET/CT has been developed, including 18F-fluiclovine. 18F-fluiclovine has the characteristics of fast uptake, rapid development and fast metabolism, which has a good diagnostic rate for the recurrence and metastasis of prostate cancer. However, at present, there are few researches and its security, diagnosis efficiency, and application value still need further research to verify.

Comparison of levofloxacin-based prophylaxis regimens for transrectal prostate biopsy: a prospective randomized single-center study.

To develop an optimal prophylactic regimen among Chinese patients who accept transrectal prostate biopsy. We enrolled 420 patients who accepted transrectal prostate biopsy. They were randomly classified into three groups (n = 140 for each): Group A received a single 500-mg tablet of levofloxacin without enema; group B received a single 500-mg tablet of levofloxacin plus enema; group C received 3-day levofloxacin orally plus enema. Patients were assessed if they had a febrile urinary tract infection (FUTI). The incidence of FUTI was compared among groups. Subgroup analysis was performed between patients at high and low risk of infection in each group. There were 15 cases developed FUTI: 7 (5%), 6 (4.3%), and 2 (1.4%), respectively, in groups A, B, and C. Of the 15 patients who developed FUTI, Escherichia coli was detected in blood culture in two cases. Urine culture results were all negative. FUTI patients (73.3% (11/15)) had at least one high risk factor. Subgroup analysis showed that the incidence of FUTI in group A was significantly higher than that in group C among high-risk patients. There was no statistical difference between group A and group B among both high- and low-risk patients. A single 500-mg dose of levofloxacin without enema represents excellent prophylaxis for transrectal prostate biopsy in Chinese patients at low risk of infection. For those at high risk, 3-day levofloxacin prophylaxis is the optimal regimen. Prebiopsy enema provides no clinically significant outcome advantage and is unnecessary.

Paroxetine in the treatment of premature ejaculation: a systematic review and meta-analysis.

BACKGROUND: Paroxetine is one of the selective serotonin reuptake inhibitors (SSRIs) used in the treatment of premature ejaculation (PE). However, this use is not approved in many countries. The purpose of this systematic review and meta-analysis is to review the efficacy and safety of paroxetine for PE patients. METHODS: We searched relevant randomized, controlled trials through May 2018, using PubMed, Embase and Cochrane Central Register. The main endpoint included intra-vaginal ejaculatory latency time (IELT) and side effects in the treatment of PE. Cochrane Collaboration's Revman software, version 5.3, was used for statistical analysis. RESULTS: Out of 493 unique articles, a total of 19 randomized, controlled trials (RCTs) were reviewed. Quite a few RCTs were considered to have unclear risk of bias because of limited information. Pooled outcomes suggested that paroxetine was more effective than placebo, fluoxetine and escitalopram at increasing IELT (all p < 0.05). However, there existed a high level of heterogeneity in the paroxetine vs. fluoxetine groups and the paroxetine vs. placebo groups. Comparing paroxetine with tramadol, sertraline, phosphodiesterase 5 inhibitors (PDE5Is), local lidocaine gel, behaviour therapy or dapoxetine, we found that the increase in IELT was not statistically significant between groups. Paroxetine combined with tadalafil or behaviour therapy was more efficacious than paroxetine alone (all p < 0.05). Although the side effects in the combination group were more common than in the paroxetine alone group, the most common adverse events, such as nausea, muscle soreness, palpitation and flushing, were mild and tolerable. The main limitations of this systematic review and meta-analysis were the different definitions of PE and short follow-up times. CONCLUSIONS: According to this systematic review and meta-analysis, paroxetine provided better efficacy than placebo, fluoxetine and escitalopram in the treatment of PE, with well-tolerated side effects. The combination group had better efficacy than the paroxetine alone group. TRIAL REGISTRATION: This review was reported in agreement with the PRISMA statement and was registered on PROSPERO 2018CRD42018097014 .

Chromosomal-Level Assembly of the Asian Seabass Genome Using Long Sequence Reads and Multi-layered Scaffolding.

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics.

Correction: Chromosomal-Level Assembly of the Asian Seabass Genome Using Long Sequence Reads and Multi-layered Scaffolding.

[This corrects the article DOI: 10.1371/journal.pgen.1005954.].

Gonad differentiation in zebrafish is regulated by the canonical Wnt signaling pathway.

Zebrafish males undergo a "juvenile ovary-to-testis" gonadal transformation process. Several genes, including nuclear receptor subfamily 5, group A (nr5a) and anti-Müllerian hormone (amh), and pathways such as Tp53-mediated germ-cell apoptosis have been implicated in zebrafish testis formation. However, our knowledge of the regulation of this complex process is incomplete, and much remains to be investigated about the molecular pathways and network of genes that control it. Using a microarray-based analysis of transforming zebrafish male gonads, we demonstrated that their transcriptomes undergo transition from an ovary-like pattern to an ovotestis to a testis-like profile. Microarray results also validated the previous histological and immunohistochemical observation that there is high variation in the duration and extent of commitment to the juvenile ovary phase among individuals. Interestingly, global gene expression profiling of diverging zebrafish juvenile ovaries and transforming ovotestes revealed that some members of the canonical Wnt/beta-catenin signaling pathway were differentially expressed between these two phases. To investigate whether Wnt/beta-catenin signaling plays a role in zebrafish gonad differentiation, we used the Tg (hsp70l:dkk1b-GFP)w32 line to inhibit Wnt/beta-catenin signaling during gonad differentiation. Activation of dkk1b-GFP expression by heat shock resulted in an increased proportion of males and corresponding decrease in gonadal aromatase gene (cyp19a1a) expression. The Wnt target gene, lymphocyte enhancer binding factor 1 (lef1), was also down-regulated in the process. Together, these results provide the first functional evidence that, similarly to mammals, Wnt/beta-catenin signaling is a "pro-female" pathway that regulates gonad differentiation in zebrafish.

Small-scale transcriptomics reveals differences among gonadal stages in Asian seabass (Lates calcarifer).

BACKGROUND: The Asian seabass (Lates calcarifer) is a protandrous hermaphrodite that typically matures as a male at approximately 2-4 years of age and then changes sex in subsequent years. Although several sexual maturation stages have been described histologically for both testis and ovary, the underlying gene expression profiles remain lacking. The development of a gene expression platform is therefore necessary to improve our understanding of the gonad development of this cultured teleost species. METHODS: Thirty Asian seabass gonads were collected from farms in Singapore, examined histologically and staged according to their sex and gonadal maturation status. Partial coding sequences of 24 sex-related genes were cloned using degenerate primers and were sequenced. Additional 13 cDNA sequences were obtained through next-generation sequencing. A real-time qPCR was then performed using the microfluidic-based Fluidigm 48.48 Dynamic arrays. RESULTS: We obtained 17 ovaries and 13 testes at various stages of sexual maturation. Of the 37 genes that were tested, 32 (86%) showed sexually dimorphic expression. These genes included sex-related genes, sox9, wt1, amh, nr5a2, dmrt1 and nr0b1, which showed testis-enhanced expression similar to other vertebrate species. Known male- and female-enhanced germ cells markers, which were established from studies in other species, similarly showed testis- and ovary-enhanced expression, respectively, in the Asian seabass. Three pro-Wnt signaling genes were also upregulated in the ovary, consistent with existing studies that suggested the role of Wnt signaling in ovarian differentiation in teleosts and mammals. The expression patterns of genes involved in steroidogenesis, retinoic acid metabolism, apoptosis and NF-κB signaling were also described. We were able to classify gonads according to sex and gonadal maturation stages, based on their small-scale transcriptomic profiles, and to uncover a wide variation in expression profiles among individuals of the same sex. CONCLUSIONS: The analysis of a selected set of genes related to reproduction and in sufficient number of individuals using a qPCR array can elucidate new insights into the molecular mechanisms involved in Asian seabass gonad development. Given the conservation of gene expression patterns found in this study, these insights may also help us draw parallels with other teleosts.

Slightly photo-crosslinked chitosan/silk fibroin hydrogel adhesives with hemostasis and anti-inflammation for pro-healing cyclophosphamide-induced hemorrhagic cystitis.

Cyclophosphamide is commonly used in the treatment of various cancers and autoimmune diseases, while concurrently imposing substantial toxicity on the bladder, frequently manifesting hemorrhagic cystitis. Intravesical interventions, such as hyaluronic acid supplementation, present a therapeutic strategy to reinstate bladder barrier function and alleviate the effects of metabolic toxicants. However, it remains a great challenge to achieve efficient cyclophosphamide-induced hemorrhagic cystitis (CHC) management with accelerated tissue repair owing to the low wet-adhesion, poor hemostasis, and acute inflammatory responses. To address these issues, a hemostatic and anti-inflammatory hydrogel adhesive of chitosan methylacryloyl/silk fibroin methylacryloyl (CHMA/SFMA) is developed for promoting the healing of CHC. The obtained hydrogels show a high adhesive strength of 26.21 N/m with porcine bladder, facilitating the rapid hemostasis within 15 s, and reinstate bladder barrier function. Moreover, this hydrogel adhesive promotes the proliferation and aggregation of SV-HUC-1 and regulates macrophage polarization. Implanting the hydrogels into CHC bladders of a SD rat model, they not only can be completely biodegraded in 14 days, but also effectively control hematuria and inflammation, and accelerate angiogenesis, thereby significantly promote the healing of bladder injury. Overall, CHMA/SFMA hydrogels exhibit rapid hemostasis for treating CHC and accelerate muscle tissue repair via angiogenesis and inflammation amelioration, which may provide a new path for managing severe hemorrhagic cystitis in the clinics.

Construction of a layer-by-layer self-assembled rosemarinic acid delivery system on the surface of CFRPEEK implants for enhanced anti-inflammatory and osseointegration activities.

Carbon fiber-reinforced polyether ether ketone (CFRPEEK) implants have attracted widespread attention in the field of clinical bone defect repair. However, the surface bioinertness confines the application of CFRPEEK implants. Inspired by the study of rosmarinic acid (RA)-promoted osteogenic differentiation, a self-assembly surface modification method based on electrostatic interactions, involving deposition of sodium carboxymethyl cellulose/chitosan and rosmarinic acid layer by layer on the surface of poly-L-lysine modified hydroxy CFRPEEK (SCPP/CC5@RA), is proposed to introduce RA on the surface of CFRPEEK for bioactivation. After layer-by-layer self-assembly (LBL), the surface of SCPP/CC5@RA exhibits weak electrophoresis (11.43 eV), suitable hydrophilicity, and bioactivity. The results of in vitro studies indicate that the RA release behavior of SCPP/CC5@RA effectively regulates the immune-inflammatory response and promotes the differentiation of osteoblasts. The rapid release of RA (0.17 µg mL-1) in the initial stage can downregulate the secretion of inflammation-related cytokines and significantly reduce oxidative stress levels; the sustained release of RA (0.06 µg mL-1) in the late stage can upregulate the expression of osteogenesis-related genes and induce mineralization of osteoblasts. Moreover, the rabbit tibia defect model demonstrates that the LBL technique can enhance the osseointegration of CFRPEEK implants. Compared with the control group, the bone trabecular thickness of the SCPP/CC5@RA group increases by 1.36 times, and the maximum pushing force increases by 2.67 times. In summary, this study provides a promising LBL based RA delivery system for the development of a dual-functional CFRPEEK implant in the field of bone implant biomaterials.

Proteomic Identification of Small Extracellular Vesicle Proteins LAMB1 and Histone H4 for Prostate Cancer Diagnosis and Risk Stratification.

Diagnosis and stratification of prostate cancer (PCa) patients using the prostate-specific antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness of tissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identified from PCa cell lines using label-free LC-MS/MS proteomics. These biomarkers underwent further validation with plasma and urine samples from different PCa stages through parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA. Additionally, a tissue microarray containing cancerous and noncancerous tissues is screened to provide additional evidence of selected sEV proteins associated with cancer origin. Results indicate that sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localised PCa patients and control subjects, while sEV protein Histone H4 is highly expressed in human urine of high-risk PCa patients compared to low-risk PCa patients and control subjects. These two sEV proteins demonstrate higher specificity and sensitivity than the PSA test and show promise for metastatic PCa diagnosis, progression monitoring, and risk stratification.

Quantification of underivatized amino acids in solid beverages using high-performance liquid chromatography and a potentiometric detector.

The simultaneous quantification of amino acids (AAs) in solid beverages without prior derivatization was explored by high-performance liquid chromatography (HPLC) coupled to a potentiometric detector. Included were threonine, leucine, methionine, phenylalanine, and histidine. The potentiometric detector was made consisting of a copper(II)-selective electrode based on a polyvinyl chloride (PVC) membrane, and the potential changes in the detector were determined according to the coordination interactions between cupric copper ions released from the inner filling solution of the electrode and AAs. Conditions were optimized for effective separation and sensitive detection. Fundamental characteristics such as linearity, limits of detection, limits of quantitation, accuracy, precision, and robustness were validated experimentally. The calibration curves showed a linear relationship between peak heights and the injection concentrations of the AAs. The detection limits down to the sub-micromolar range were achieved under isocratic conditions, outperforming ultraviolet detection. The copper(II)-selective electrode had a minimum lifetime of one month. Some real samples were examined to further demonstrate the feasibility of the proposed approach. The measurement results obtained by the present method were in good agreement with those obtained by the HPLC-mass spectrometry (MS), indicating that the combined HPLC-potentiometric method is a potential option for quantifying AAs.

Eph receptor B6 shapes a cold immune microenvironment, inhibiting anti-cancer immunity and immunotherapy response in bladder cancer.

Background: The role of Eph receptors and related ephrin (EFN) ligands (as the largest family of transmembrane-bound RTKs) in immunomodulation in many types of cancer, especially bladder cancer (BLCA), is scarcely known. Methods: A pan-cancer dataset was retrieved from The Cancer Genome Atlas (TCGA) to explore the relation between Eph receptor/EFN ligand family genes and immunomodulators and tumor-infiltrated immune cells (TIICs). Local BLCA, GSE32894, and GSE31684 cohorts were applied to validate. The IMvigor210 cohort was employed to explore the relationship between EPHB6 and immunotherapy response. Moreover, association between EPHB6 and molecular subtype was investigated to explore potential therapeutic strategies. Immunohistochemical staining of CD8 and CD68 was performed to validate the correlation between EPHB6 and TIICs. Results: The pan-cancer analysis revealed variations in the immunological effects of Eph receptor/EFN ligand family genes across different types of cancer. EPHB6 expression negatively correlated with the expression of the majority of immunomodulators (including HLA and immune checkpoints), and CD8 T cells and macrophages in both the TCGA-BLCA and validation BLCA cohorts, shaping a cold immune microenvironment with inhibited immunity. In the IMvigor210 cohort, patients with high-EPHB6 highly correlated with a non-inflamed, low PD-L1 expression immune phenotype, and correspondingly, with less responders to immunotherapy. The high-EPHB6 group, enriched with the basal subtype, presented significantly fewer TP53 and more FGFR3 genomic alterations. Finally, a novel EPHB6-related Genes signature, with reliable and robust ability in prognosis prediction, was constructed. Conclusions: This study comprehensively investigated the immunological effects of Eph receptor/EFN ligand family genes pan-cancer, and specially identified the immunosuppressive role of EPHB6 in BLCA. Furthermore, EPHB6 may predict the molecular subtype and prognosis of BLCA, and serve as a novel therapeutic target to improve the sensitivity of immunotherapy.

Feasibilities and outcomes of patients treated with simultaneous prostate biopsy and general urological surgeries.

The present single-center retrospective clinical real-world study aimed to assess the feasibility and outcomes of patients who underwent simultaneous prostate biopsy and general urological surgeries. The medical records of 49 patients who underwent prostate biopsy and general urological surgeries simultaneously from October 2016 to June 2019 were retrospectively reviewed. Patients' outcomes were evaluated 3 days, 1 month and 6 months after biopsy. Of the 49 biopsy cases, 41 were treated by transurethral prostatectomy, two by ureteroscopic lithotripsy, two by laparoscopic renal cyst decortication, two by cystostomy and two by ureteral stent extraction. The overall detection rate of clinically significant prostate cancer was 22.4%. The rate in patients with a prostate imaging reporting and data system (PI-RADS) score of 4-5 was 100%, while in cases with a PI-RADS score of <3 it was 7.1%. Postoperative complications within 3 days included hematuria in 39 (79.6%) cases, fever in three (6.1%) cases and hematochezia in two (4.1%) cases. There was no significant difference in the incidence of hematuria between the transrectal and transperineal approaches; however, the overall incidence of complications was significantly reduced after switching from a transrectal approach to a transperineal approach. No complications were observed after 1 or 6 months. In summary, combining simultaneous prostate biopsy to general urological surgeries is a safe and feasible approach. The transperineal approach has a lower incidence of complications. This method may benefit certain patients who are concurrently undergoing general urological surgeries and are under suspicion of prostate cancer in real-world clinical practice.

Construction of Multifunctional Zinc Ion Sustained-Release Biocoating on the Surface of Carbon Fiber Reinforced Polyetheretherketone with Enhanced Anti-inflammatory Activity, Angiogenesis, and Osteogenesis.

Current treatments of carbon fiber-reinforced polyetheretherketone (CFRPEEK) as orthopedic implants remain unsatisfactory due to the bioinert surface. The multifunctionalization of CFRPEEK, which endows it with regulating the immune inflammatory response, promoting angiogenesis, and accelerating osseointegration, is critical to the intricate bone healing process. Herein, a multifunctional zinc ion sustained-release biocoating, consisting of a carboxylated graphene oxide, zinc ion, and chitosan layer, covalently grafts on the surface of amino CFRPEEK (CP/GC@Zn/CS) to coordinate with the osseointegration process. The release behavior of zinc ions theoretically conforms to the different demands in the three stages of osseointegration, including the burst release of zinc ions in the early stage (7.27 µM, immunomodulation), continuous release in the middle stage (11.02 µM, angiogenesis), and slow release in the late stage (13.82 µM, osseointegration). In vitro assessments indicate that the multifunctional zinc ion sustained-release biocoating can remarkably regulate the immune inflammatory response, decrease the oxidative stress level, and promote angiogenesis and osteogenic differentiation. The rabbit tibial bone defect model further confirms that, compared to the unmodified group, the bone trabecular thickness of the CP/GC@Zn/CS group increases 1.32-fold, and the maximum push-out force improves 2.05-fold. In this study, a multifunctional zinc ion sustained-release biocoating constructed on the surface of CFRPEEK that conforms to the requirements of different osseointegration stages can be an attractive strategy for the clinical application of inert implants.

Ag NC and Ag NP/PorC Film-Based Surface-Enhanced Raman Spectroscopy-Type Immunoassay for Ultrasensitive Prostate-Specific Antigen Detection.

Surface-enhanced Raman scattering (SERS) is a spectral detection technology with high sensitivity and detectivity and can be used to detect the fingerprint information of the molecules with ultralow concentration. Herein, a kind of immunostructure constructed by Ag nanoparticle/porous carbon (Ag NP/PorC) films as the immunosubstrate and Ag NCs as the immunoprobes was presented for ultralow level prostate-specific antigen (PSA) detection. Experimentally, the Ag NP/PorC film was first prepared with a facile method by carbonizing the gelatin-AgNO3 film in air, and Ag NCs were synthesized by the hydrothermal method. Then, the Ag NP/PorC film was modified by PSA antibodies as the substrate, while Ag NCs were decorated by R6G and PSA antibodies for probes. The sandwiched SERS detection embodiment was constructed by the immunoreaction between the PSA and PSA antibody predecorated on the substrate and probes. Our results show that the proposed SERS-type immunoassay is highly sensitive and selective to a wide range of PSA concentrations from 10-5 to 10-12 g/mL. Thereafter, it was also implemented to detect the PSA level in human serum, and the results successfully reproduce the PSA levels as those measured by the chemiluminescence method with a recovery rate above 90%. All in all, this SERS-type immunoassay provides a promising method for the early diagnosis of prostate cancer.

Pelvic drain placement after robot-assisted radical prostatectomy: meta-analysis.

BACKGROUND: It is not clear whether the routine placement of a pelvic drain after robot-assisted radical prostatectomy is a necessity. The aim of this study was to investigate this through a meta-analysis of RCTs and non-randomized studies. METHODS: A search was performed in PubMed/MEDLINE, Embase, the Cochrane Library, and the Web of Science, up to 9 March 2023, for clinical trials comparing no drain with pelvic drain placement for patients with prostate cancer after robot-assisted radical prostatectomy. Two researchers independently conducted literature screening, data extraction, and quality assessment. A random-effect model was assumed for all analyses. The Cochrane Collaboration's risk-of-bias tool was used to evaluate the methodological quality of RCTs and, for non-randomized studies, the ROBINS-I tool was used (where ROBINS-I stands for Risk Of Bias In Non-randomized Studies - of Interventions). This meta-analysis was prospectively registered in PROSPERO, the international prospective register of systematic reviews (CRD42023406429). RESULTS: A total of six studies with 1480 patients were included in the meta-analysis. Both the meta-analysis of RCTs and the meta-analysis of non-randomized studies showed that patients without drains had a similar estimated blood loss (mean difference 40.49 ml, 95% c.i. -59.75 to 140.74 ml, P = 0.430, and mean difference -14.20 ml, 95% c.i. -32.26 to 3.87 ml, P = 0.120 respectively), overall complication rate (OR 0.60, 95% c.i. 0.35 to 1.04, P = 0.070, and OR 0.90, 95% c.i. 0.59 to 1.39, P = 0.640 respectively), Clavien-Dindo grade I-II complication rate (OR 0.62, 95% c.i. 0.34 to 1.13, P = 0.120, and OR 0.83, 95% c.i. 0.28 to 2.51, P = 0.750 respectively), Clavien-Dindo grade III-V complication rate (OR 0.60, 95% c.i. 0.10 to 3.69, P = 0.590, and OR 0.92, 95% c.i. 0.25 to 3.39, P = 0.900 respectively), and duration of hospital stay (mean difference -0.08 days, 95% c.i. -0.45 to 0.29 days, P = 0.670, and mean difference -0.64 days, 95% c.i. -2.67 to 1.39 days, P = 0.540 respectively) compared with routinely drained patients. Meta-analysis of non-randomized studies revealed that the duration of operation for patients without drains was shorter than that for patients with drains (mean difference -34.88 min, 95% c.i. -43.58 to -26.18 min, P < 0.001), but the meta-analysis of RCTs indicated that there was no significant difference between the two groups (mean difference -7.64 min, 95% c.i. -15.61 to 0.32 min, P = 0.060). CONCLUSION: The intraoperative and postoperative outcomes of patients without drains were not inferior to those of patients with drains. In selected patients, pelvic drains can be omitted after robot-assisted radical prostatectomy.