Comparative effectiveness of multiple androgen receptor signaling inhibitor medicines with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer: a study in the real world.

Background: The current treatment strategy for metastatic Hormone-Sensitive Prostate Cancer (mHSPC) is the combination of Androgen Receptor Signaling Inhibitors (ARSIs) medicines with androgen deprivation therapy (ADT). However, there is a lack of real-world data comparing the efficacy of different ARSI pharmaceuticals. Therefore, the objective of this study was to compare the effectiveness and safety of bicalutamide, abiraterone, enzalutamide, and apalutamide in combination with ADT for patients with mHSPC. Methods: We retrospectively analyzed 82 patients diagnosed with mHSPC, including 18 patients treated with abiraterone acetate with prednisone, 21 patients with enzalutamide, 20 patients with apalutamide, and 23 patients with bicalutamide. We evaluated PSA progression-free survival (PSA-PFS), imaging progression-free survival (r PFS), castration resistance progression-free survival (CRPC-PFS), and overall survival (OS) using Kaplan-Meier survival analyses. Additionally, we explored relevant factors affecting prognosis through univariate and multivariate Cox risk-proportionality models. PSA response rates at 3, 6, and 12 months, nadir PSA levels (nPSA), and time to nadir (TTN) in different medication subgroups after treatment were documented, and we used one-way ANOVA to determine the effect of these measures on patient prognosis. Results: In comparison with bicalutamide, both enzalutamide and apalutamide have shown significant advantages in delaying disease progression among mHSPC patients. Specifically, enzalutamide has been found to significantly prolong PSA-PFS (HR 2.244; 95% CI 1.366-3.685, p=0.001), rPFS (HR 2.539; 95% CI 1.181-5.461; p= 0.007), CRPC-PFS (HR 2.131; 95% CI 1.295-3.506; p= 0.003), and OS (HR 2.06; 95% CI 1.183-3.585; P=0.005). Similarly, apalutamide has significantly extended PSA-PFS (HR 5.071; 95% CI 1.711-15.032; P= 0.003) and CRPC-PFS (HR 6.724; 95% CI 1.976-22.878; P=0.002) among patients. On the other hand, the use of abiraterone in combination with ADT did not demonstrate a significant advantage in delaying diseases progression when compared with the other three agents in mHSPC patients. There were no significant differences in overall adverse event rates among the four pharmaceuticals in terms of safety. Additionally, the observation of PSA kinetics revealed that enzalutamide, apalutamide, and abiraterone acetate had a significant advantage in achieving deep PSA response (PSA ≤ 0.2 ng/ml) compared with bicalutamide (p=0.007 at 12 months). Enzalutamide and apalutamide exhibited preeminence efficacy, with no substantial difference observed between the two medications. Conclusions: Abiraterone, enzalutamide, and apalutamide were found to significantly reduce and stabilize PSA levels in mHSPC patients more quickly and thoroughly than bicalutamide. Furthermore, enzalutamide and apalutamide were found to significantly prolong survival and delay disease progression in mHSPC patients compared with bicalutamide. It should be noted that abiraterone did not demonstrate a significant advantage in delaying disease compared with enzalutamide and apalutamide. After conducting drug toxicity analyses, it was determined that there were no significant differences among the four drugs.

Risk factors of high fluid absorption in patients treated with mini-PCNL: a single-center prospective study.

BACKGROUND: The factors influencing fluid absorption in mini-percutaneous nephrolithotripsy (mini-PCNL) are still unknown. We aim to investigate the factors that influence irrigation fluid absorption during mini-PCNL. METHODS: A total of 94 patients who underwent mini-PCNL were included in this prospective study. The endoscopic surgical monitoring system (ESMS) was used to measure the volume of irrigation fluid absorbed during the procedure. Irrigating time, the total volume of irrigation fluid, stone size, S.T.O.N.E. score, hemoglobin, electrolyte levels, and postoperative complications were recorded. RESULTS: A significant correlation was observed between fluid absorption and the presence of postoperative fever, and based on this phenomenon, patients were divided into low and high fluid absorption groups. The serum creatinine level in the high fluid absorption group was significantly high (7 vs. 16.5, p = 0.02). Significant differences were observed between the low and high fluid absorption groups in terms of mean stone size (21.70 mm vs. 26.78 mm), presence of stone burden ≥ 800 mm2 (4% vs. 23%), S.T.O.N.E. score > 8 (4% vs. 38%), the fluid used > 18,596 ml (19% vs. 78%), irrigation time (55.61 min vs. 91.28 min), and perfusion rate (24% vs. 45%) (all p < 0.05). The rates of postoperative fever and SIRS in the high fluid absorption group were significantly high (p < 0.05). CONCLUSIONS: Mean stone size, presence of stone burden ≥ 800 mm2, S.T.O.N.E. score > 8, the fluid used > 18596 mL, irrigation time, and perfusion rate are risk factors of intraoperative fluid absorption in mini-PCNL.

IN VITRO EVALUATION OF A NOVEL AUTOMATIC INTRAOPERATIVE BLOOD LOSS MONITOR.

INTRODUCTION: Accurate and real-time monitoring of surgical blood loss is essential for ensuring intraoperative safety. However, there is currently no standard way to assess the amount of blood lost in patients during surgery. This study aims to evaluate the accuracy and precision of a new automatic intraoperative blood loss monitor, which can measure both free blood volume and blood content in sponges in real time. METHODS: The monitor uses an integrated photoelectric probe to gauge hemoglobin levels in both free blood and blood taken from surgical sponges. This data, combined with initial hemoglobin levels, is processed using specific calculations to determine blood volume. We created 127 diverse free blood samples and 160 blood-containing sponge samples by utilizing fresh pig blood and physiological saline. The monitor then measured these samples. We subsequently compared its measurements with actual values acquired through physical measurements, detecting both agreement and measurement errors. Repeated measurements were performed to calculate the coefficient of variation, thereby evaluating the monitor's precision. RESULTS: The estimated blood loss percentage error of the monitor was 5.2% for free blood, -5.7% for small sponge, -6.3% for medium sponge, and -6.6% for large sponge. The coefficient of variation of free blood with different hemoglobin concentrations measured by the monitor was less than 10%. Bland-Altman analysis showed that the limits of agreement between the monitor and the reference method were all within the acceptable clinical range. CONCLUSION: The new automatic intraoperative blood loss monitor is an accurate and reliable device for monitoring both free blood and surgical sponge blood, and shows high performance under various clinical simulation conditions.

Biomimetic single Al-OH site with high acetylcholinesterase-like activity and self-defense ability for neuroprotection.

Neurotoxicity of organophosphate compounds (OPs) can catastrophically cause nervous system injury by inhibiting acetylcholinesterase (AChE) expression. Although artificial systems have been developed for indirect neuroprotection, they are limited to dissociating P-O bonds for eliminating OPs. However, these systems have failed to overcome the deactivation of AChE. Herein, we report our finding that Al3+ is engineered onto the nodes of metal-organic framework to synthesize MOF-808-Al with enhanced Lewis acidity. The resultant MOF-808-Al efficiently mimics the catalytic behavior of AChE and has a self-defense ability to break the activity inhibition by OPs. Mechanism investigations elucidate that Al3+ Lewis acid sites with a strong polarization effect unite the highly electronegative -OH groups to form the enzyme-like catalytic center, resulting in superior substrate activation and nucleophilic attack ability with a 2.7-fold activity improvement. The multifunctional MOF-808-Al, which has satisfactory biosafety, is efficient in reducing neurotoxic effects and preventing neuronal tissue damage.

Hazardous toxic metal(loid)s in top- and deep-soils during the transformation of aquaculture ponds restored to farmland.

The pollution risks due to the soil migration of toxic metal(loid)s (TMs) are a greatly hazard to ecological environment as well as animal and human health. Previous studies have primarily focused on surface contamination while deep soil layers often contain dangerous levels of TMs. We used restored wheat and rice farmlands from aquaculture ponds as a case study to examine the ecological risk and distribution of TMs in soil profiles. The elements Cu, Zn, Cr, Cd, Hg and As were markedly enriched in the 60-180 cm soil layers of restored farmland, and their concentrations decreased in the several depths as follows: 120-180 cm > 60-120 cm > 0-60 cm. Concentrations of TMs were 9.5-128 % greater in the restored farmlands relative to farmlands not exposed to aquaculture practices. Cadmium and mercury were the most serious contaminants and increased the overall ecological risk. The subsoil of wheat farming system had the highest pollution risk versus the restored rice farmland at 60-120 cm due to elevated levels of Cu, Zn and Pb. Toxic metal(loid)s might be derived from natural sources in deep soil of conventional farmland whereas aquaculture practices were found to constitute the major contribution in the subsoil of restored farmland. Our results indicated that the TMs that were buried in deep soil layers migrated upward and were a significant pollution risk. Urgent actions should be taken to identify and alleviate the contamination sources of these deep soils in addition to the conventional leaching and migration processes of surface contaminants.

Ultrasound-assisted modified paramedian technique for spinal anesthesia in elderly.

BACKGROUND: At present, there are two techniques which are widely applied clinically; the midline and the paramedian. Both methods are difficult for clinicians when treating the elderly. The aim of this work is to explore the feasibility of an ultrasound-assisted modified paramedian technique for spinal anesthesia in the elderly. This would provide clinicians with a new and easy-to-operate technique. METHODS: A total of 150 elderly patients who were scheduled for urology surgery under spinal anesthesia in our hospital were randomly divided into three groups (n = 50): (i) midline technique group (group M), (ii) paramedian technique group (group P), and (iii) modified paramedian technique group (group PM). All spinal anesthesia were performed by the same second-year resident. RESULTS: Compared with groups M and P, group PM had significantly higher first-attempt success rate (P < 0.05, especially in patients aged 65-74 years), fewer attempts (P < 0.05), and higher patient satisfaction score (P < 0.05). Compared with group M, the time taken to perform spinal anesthesia and the number of needle redirections were significantly reduced in group PM (P < 0.05). There was no statistically significant difference between groups PM and P. There were also no statistically significant differences in the cases of inconsistency between ultrasound-assisted and landmark-guided location of intervertebral space, the time taken to ultrasound-assisted location, the onset time to pain block at T10, the incidence of hypotension, anesthesia effect and the incidence of headache, lower back pain, or nausea and vomiting, within 24 h after surgery. CONCLUSIONS: The modified paramedian technique in spinal anesthesia for elderly patients can significantly improve the first-attempt success rate, reduce both the number of attempts and procedure time, and minimize tissue damage during the operation. Compared with the traditional techniques, the modified paramedian technique combines the advantages of both the midline and the paramedian methods, and is easy to learn. It is worthy of further research and application. TRIAL REGISTRATION: Prospectively registered at the China Clinical Trial Registry, registration number ChiCTR2100047635 , date of registration: 21/06/2021.

[Involvement of cAMP-PKA pathway in group â ¡ metabotropic glutamate receptors-mediated regulation of respiratory rhythm from neonatal rat brainstem slice].

The study aims to identify the role of cAMP-PKA pathway in the group Ⅱ metabotropic glutamate receptors (mGluRs)-mediated regulation of respiratory rhythm from the brainstem slice. Neonatal (aged 0-3 d) Sprague-Dawley rats of either sex were used. The brainstem slice containing the medial region of the nucleus retrofacialis (mNRF) and the hypoglossal nerve rootlets was prepared, and the surgical procedure was performed in the modified Kreb's solution (MKS) with continuous carbogen (95% O2 and 5% CO2) bubbling, and ended in 3 min. Respiratory rhythmical discharge activity (RRDA) of the hypoglossal nerve rootlets was recorded by suction electrode. Eighteen brainstem slice preparations were divided into 3 groups. In group 1, group Ⅱ mGluRs specific antagonist (2S)-α-ethylglutamic acid (EGLU) was added into the perfusion solution for 10 min. In group 2, after application of Forskolin for 10 min, washout with MKS, the slice was perfused with Rp-cyclic 3', 5'-hydrogen phosphorothioate adenosine triethylammonium salt (Rp-cAMPS) alone for another 10 min. In group 3, after application of Rp-cAMPS for 10 min, additional EGLU was added into the perfusion for another 10 min. The results showed EGLU shortened respiratory cycle (RC), but the changes of integral amplitude (IA) and inspiratory time (TI) were not statistically significant. Forskolin induced significant decreases in RC, and increased TI, IA. Rp-cAMPS could make the opposite effect compared with the changes of RRDA with Forskolin. The effect of EGLU on the RRDA was inhibited after blocking the cAMP-PKA pathway. Taken together, cAMP-PKA pathway may play an important role in the group Ⅱ mGluRs-mediated regulation of RRDA in the brainstem slice of neonatal rats.

[Group II metabotropic glutamate receptors is involved in the modulation of respiratory rhythmical discharge activity in neonatal rat medullary brain slices].

OBJECTIVE: To explore the role of group II metabotropic glutamate receptors in the modulation of basic respiratory rhythm. METHODS: Neonatal (0-3 days) SD rats of either sex were used. The medulla oblongata brain slice containing the medial region of the nucleus retrofacialis (mNRF) and the hypoglossal nerve rootlets was prepared, and the surgical procedure was performed in the modified Kreb's solution (MKS) with continuous carbogen (95% O2 and 5% CO2) within 3 min. The brain slices were quickly transferred to a recording chamber and continuously perfused with oxygen-saturated MKS at a rate of 4-6 ml/min at 27-29 degrees celsius. Eighteen medulla oblongata slices were divided into 3 groups and treated for 10 min with group II metabotropic glutamate receptor-specific agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (APDC) (at concentrations of 10, 20, 50 micromol/L), group II metabotropic glutamate receptor antagonist (2S)-alpha-ethylglutamic acid (EGLU) (300 micromol/L), or APDC (50 micromol/L)+EGLU (300 micromol/L) after a 10 min APDC (50 micromol/L) application. Respiratory rhythmical discharge activity (RRDA) of the rootlets of the hypoglossal nerve was recorded by suction electrodes. RESULTS: APDC produced a dose-dependent inhibitory effect on the RRDA, prolonging the respiratory cycle and expiratory time and decreasing the integral amplitude and inspiratory time. EGLU induced a significant decrease in the respiratory cycle and expiratory time. The effect of APDC on the respiratory rhythm was partially reversed by the application of APDC+EGLU. CONCLUSION: Group II metabotropic glutamate receptors are probably involved in the modulation of the RRDA in isolated neonatal rat brainstem slice.