Evaluating first-line therapeutic strategies for metastatic castration-resistant prostate cancer: a comprehensive network meta-analysis and systematic review.

Objective: This study aimed to evaluate the relative efficacy and safety of first-line treatment options for metastatic castration-resistant prostate cancer (mCRPC). Methods: We systematically searched electronic databases, including PubMed and Web of Science, for studies published from their inception to April 3rd, 2023. Inclusion criteria were: 1) Completed Phase III or IV randomized controlled trials (RCTs) registered on ClinicalTrials.gov; 2) Patients with a confirmed diagnosis of mCRPC who had not previously received chemotherapy or novel endocrine therapies. We conducted a network meta-analysis using R software (version 3.4.0). Network graphs and risk of bias graphs were generated using Stata 14.0 and RevMan 5.4, respectively. The primary outcome was overall survival (OS), and the secondary outcome was the incidence of severe adverse events (SAEs). Results: Seven RCTs encompassing 6,641 patients were included. The network meta-analysis revealed that both docetaxel+prednisone (DP) and cabazitaxel+prednisone (CP) significantly improved OS compared to abiraterone. Compared to placebo, DP showed comparable results to both cabazitaxel 20 mg/m^2+prednisone (C20P) and cabazitaxel 25 mg/m^2+prednisone (C25P) in terms of OS. For SAEs, both DP and C20P were superior to C25P, with no statistical difference between C20P and DP. The probability ranking plots indicated that C25P ranked highest for OS, while DP ranked highest for SAEs. Conclusions: Based on our network meta-analysis, we recommend cabazitaxel 20 mg/m^2+prednisone (C20P) as the primary choice for first-line management of mCRPC, followed by DP. Enzalutamide and abiraterone are suggested as subsequent options. Radium-223 may be considered for patients presenting with bone metastases. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023443943.

Sensitizers of Metal Complexes with Sulfur Coordination Achieving a Power Conversion Efficiency of 12.89.

In the study to improve the light absorption range and intensity of dye sensitizers in the visible region and promote their photovoltaic performance, five novel polymeric metal complexes with sulfur coordination (BDTT-VBT-Ni, BDTT-VBT-Cu, BDTT-VBT-Zn, BDTT-VBT-Cd, and BDTT-VBT-Hg) to be used as D-A-π-A motif dye sensitizers were designed, synthesized, and characterized. In these polymeric metal complexes with sulfur coordination, the metal complexes with sulfur coordination of benzodithiophene derivatives are used as auxiliary electron acceptors, 8-quinolinol derivatives are used as π-bridge and electron acceptors, and thienylbenzene-[1,2-b:4,5-b'] dithiophene (BDTT) are used as electron donors. The effect of different metal complexes with sulfur coordination on the photovoltaic performance of dye sensitizers has been systematically studied. Under AM 1.5 irradiation (100 mW cm-2), the devices of dye-sensitized solar cells (DSSCs) based on five polymeric metal complexes with sulfur coordination exhibited a short-circuit current density (Jsc) of 13.43, 15.07, 18.00, 18.99, and 20.78 mA cm-2, respectively, and their power conversion efficiencies (PCEs) were 7.10, 8.59, 10.68, 11.23, and 12.89%, respectively, and their thermal decomposition temperatures (Td) were 251, 257, 265, 276, and 277 °C, respectively. The result shows that the Jsc and PCE of five polymeric metal complexes increase by degrees, and the PCE of BDTT-VBT-Hg is up to 12.89%, which is because of the strength of the coordination bonds between Ni(II), Cu(II), Zn(II), Cd(II), and Hg(II) and sulfur increases in turn so that the electron-withdrawing ability and electron-transfer ability of auxiliary electron acceptors is enhanced. These results provide a new way to develop stable and efficient metal complexes with sulfur coordination dye sensitizers in the future.

Application of laser speckle blood perfusion imaging in the evaluation of erectile function in rats.

Intracavernosal pressure measurement is the gold standard for evaluating erectile function in experimental animals, but it has the shortcoming of being invasive. This study aimed to explore the application of laser speckle perfusion imaging in evaluating erectile function in rats. Sixty Sprague Dawley rats were randomly divided into the sham operation and model groups (n = 30 each). A rat model of neuroinjury erectile dysfunction was established by surgically damaging the bilateral cavernous nerves in the model group. Simulated surgery was performed in the sham operation group; the nerves were not damaged. Erectile function was evaluated by comparing the changes in intracavernosal pressure and blood flow fluctuations when the cavernous nerve was stimulated using the same voltage parameters. Intracavernosal pressure in the model group was significantly lower than that in the other group when using 2.5 V. No significant difference was found in cavernous blood flow fluctuation between the two groups when using 0.5 V. Cavernous blood flow fluctuation in the model group after 2.5 V, 5 V and 7.5 V stimulations was significantly lower than that in the sham operation group. Evaluating erectile function in rats is feasible by measuring the cavernous blood flow using laser speckle perfusion imaging.

[Hongjing-1 Recipe maintains the expression level of Connexin43 in the penile tissue of SD rats with bilateral cavernous nerve injury].

OBJECTIVE: To explore the effects of Hongjing-1 Recipe (HJ-1) on erectile function and the expression of the gap junction protein Connexin43 (Cx43) in the penile tissue in male rats with bilateral cavernous nerve injury (BCNI). METHODS: Fifty male SD rats were randomly divided into five groups of an equal number: sham operation, BCNI model control, and low-, medium- and high-dose HJ-1. The BCNI model was made in the latter four groups by clamping the bilateral cavernous nerves with hemostatic forceps. Three days after modeling, the rats in the sham operation and BCNI model control groups were treated intragastrically with pure water and those in the low-, medium- and high-dose HJ-1 groups with HJ-1 at 2.835, 5.67 and 11.34 g/kg/d, respectively, all for 28 successive days. Then, the animals were subjected to intracavernous pressure (ICP) measurement for evaluation of their erectile function and immunofluorescence staining and Western blot for determination of the Cx43 level in the penile tissue. RESULTS: The BCNI model controls, compared with the rats in the sham operation group, showed a dramatically decreased ratio of maximum ICP to mean arterial pressure (mICP/MAP) (0.40 ± 0.04 vs 0.83 ± 0.10, P < 0.01) and that of total ICP to MAP (tICP/MAP) (21.89 ± 2.16 vs 50.27 ± 4.45, P < 0.01), as well as a down-regulated expression of Cx43 in the penile tissue (P < 0.01). In comparison with the rats in the BCNI model control group, those in the medium- and high-dose HJ-1 groups exhibited significantly increased ratios of mICP/MAP (0.54 ± 0.05, P < 0.05; 0.61 ± 0.06, P < 0.01) and tICP/MAP (31.20 ± 3.85, P < 0.01; 37.82 ± 4.17, P < 0.01) and up-regulated expression of Cx43 (P<0.05 and P<0.01). CONCLUSIONS: Hongjing-1 Recipe can effectively improve ED in rats with bilateral cavernous nerve injury, which may be attributed to its effect of maintaining the expression level of the gap junction protein Cx43 in the penile tissue.

Borromean Droplet in Three-Component Ultracold Bose Gases.

We investigate droplet formation in three-component ultracold bosons. In particular, we identify the formation of a Borromean droplet, where only the ternary bosons can form a self-bound droplet while any binary subsystems cannot, as the first example of Borromean binding due to a collective many-body effect. Its formation is facilitated by an additional attractive force induced by the density fluctuation of a third component, which enlarges the mean-field collapse region in comparison to the binary case and renders the formation of a Borromean droplet after incorporating the repulsive force from quantum fluctuations. Outside the Borromean regime, we demonstrate an interesting phenomenon of droplet phase separation due to the competition between ternary and binary droplets. We further show that the transition between different droplets and gas phase can be conveniently tuned by boson numbers and interaction strengths. The study reveals the rich physics of a quantum droplet in three-component boson mixtures and sheds light on the more intriguing many-body bound state formed in multicomponent systems.

Neuroprotective effect of Hongjing I granules on erectile dysfunction in a rat model of bilateral cavernous nerve injury.

Neurogenic erectile dysfunction (NED) is an inevitable postoperative disease of cavernous nerve injury which will lead to various pathophysiological changes in the corpus cavernosum and dorsal penile nerve caused by radical prostatectomy (RP). Although serval years of clinical application of HJIG I granules (HJIG), an innovative formulation, has demonstrated its reliable clinical efficacy against NED, the mechanism of HJIG remains unclear. This study aimed to assess the neuroprotective effect of HJIG, to repair damaged nerves in a rat model of bilateral cavernous nerve injury (BCNI) in vivo and their effects on neurites of major pelvic ganglia (MPG) regeneration and Schwann cells (SCs) proliferation in vitro. Rats were divided into five groups randomly: normal control (NC), BCNI-induced ED model (M), M + low-dose HJIG (HL), M + medium-dose HJIG (HM), and M + high-dose HJIG (HH). All groups were treated with normal saline or the relevant drug for 28 consecutive days after a standard NED animal model. Our data revealed that administration of HJIG improved NED that was detected by intracavernous pressure (ICP) in a dose-dependent manner. The haematoxylin-eosin (HE) and Immunofluorescence (IF) staining demonstrated that HJIG ameliorate the shape of penis and induced the protein synthesis of GAP43, NF200, S100, and nNOS. NF200 and S100 level were also detected by western blotting. Moreover, HJIG (0.78 mg/mL) markedly increased SCs viability and promoted neurites regeneration of MPG. These findings provide new insights into the NED therapy by HJIG.

Effect of HongJing I in Treating Erectile Function and Regulating RhoA Pathway in a Rat Model of Bilateral Cavernous Nerve Injury.

HongJing I (HJI), a traditional Chinese herbal formula, has been confirmed to be effective for the clinical treatment of erectile dysfunction (ED). However, the mechanism of action of HJI remains unclear. Here, we aimed to investigate the effect and underlying mechanisms of HJI against ED in a rat model of bilateral cavernous nerve injury (BCNI). Rats were divided into five groups: normal control (NC), BCNI-induced ED model (M), M + low-dose HJI (HL), M + medium-dose HJI (HM), and M + high-dose HJI (HH). All groups were treated with normal saline or the relevant drug for 28 consecutive days after inducing BCNI-ED. At the end of the treatment period, the intracavernous pressure (ICP) was recorded, and histological examination was conducted using Masson's trichrome staining. Immunofluorescence staining and western blotting were applied to detect the changes in fibrosis protein and Ras homolog A (RhoA), Rho-associated protein kinase 1 (ROCK1), and ROCK2 expression. We found that HJI effectively improved the ICP in the treatment groups. In addition, RhoA, ROCK1, and ROCK2 expression levels were increased upon BCNI-ED induction, and HJI successfully inhibited cavernosum fibrosis and the activation of RhoA/ROCK2 signaling. Overall, these results suggest that the effects of HJI in attenuating ED may be caused, at least in part, by the suppression of RhoA/ROCK2 signaling and alleviation of fibrosis. However, the precise mechanism surrounding this requires further investigation in future studies.

[Inhibitory effect of salidroside on H2O2-induced down-regulation of Cx43 expression in corpus cavernosum smooth muscle cells in rats].

OBJECTIVE: To explore the regulatory effect of salidroside on H2O2-induced decrease in the expression of the connexin43 (Cx43) protein in corpus cavernosum smooth muscle cells (CCSMC). METHODS: Rat CCSMCs were isolated, primarily cultured in vitro and identified by immunocytochemical assay. The optimum concentration of H2O2 for intervention was determined by detecting its effect on the viability of the CCSMCs and used in the treatment of the CCSMCs for different lengths of time, and meanwhile salidroside was applied at 16 µg/ml (low dose) or 64 µg/ml (high dose) for intervention. Finally, the expressions of the Cx43 protein in the CCSMCs of different groups of rats were determined by Western blot. RESULTS: The CCSMCs grew normally, with a positive rate of over 90%. At 1, 2 and 4 hours of treatment with H2O2 at the optimum concentration of 200 µmol/L, the expression of Cx43 in the CCSMCs was significantly decreased as compared with that in the blank control group (P < 0.01), even more significantly at 4 hours than at 1 and 2 (P < 0.01). Intervention with high-dose salidroside, however, markedly inhibited the down-regulation of the Cx43 expression (P < 0.05), which showed no statistically significant difference from that in the normal control group (P = 0.322 2). CONCLUSIONS: Salidroside can suppress H2O2-induced decrease in the expression of the Cx43 protein in rat CCSMCs.

Serum miRNA expression and correlation with clinical characteristics in acute kidney injury.

Acute kidney injury (AKI) is a common clinical emergency. Its fatality rate and mortality exhibit a rising trend following the increase of aging population. MiRNA participates in disease occurrence and development via targeting mRNA expression. Previous study indicated that miRNA expression was different in peripheral blood from AKT patients. However, there is still lack of related report about miRNA expression spectrum and correlation with clinical features. MiRNA microarray was applied to test miRNA expression in the serum of acute kidney injury patients. qRT-PCR was adopted to verify the differentially expressed miRNAs. Their correlation with the staging was analyzed. A total of 14 miRNAs exhibited upregulation, while 10 miRNAs presented downregulation in AKI patients compared with healthy control. Real-time PCR revealed that 14 selected miRNAs were obviously different. Correlation analysis demonstrated that miR-210, miR-21, miR-34 were positively correlated with AKI clinical staging (r = 0.56, P < 0.05; r = 0.32, P < 0.05; r = 0.38, P < 0.05, respectively). MiR-16 showed negative correlation with clinical staging (r = -0.34, P < 0.05). Multiple miRNAs were differentially expressed in the serum of AKI patients. MiR-210, miR-21, and miR-34 were correlated with AKI staging that could be treated as the biomarker of AKI.