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Background: Androgen receptor signaling inhibitors (ARSis), when administered sequentially or in combination with docetaxel and androgen deprivation therapy (ADT), have been shown to enhance overall survival (OS) and progression-free survival (PFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Nonetheless, the optimal sequence for administering chemotherapy and ARSis remains to be determined. Objective: To compare the efficacy of ARSis sequential therapy with ARSis combined therapy for mHSPC, and to evaluate the efficacy and safety of different combination regimens. Methods: The PubMed, Embase, Cochrane Central, and ClinicalTrials.gov databases were searched from their inception through 14 July 2024, to identify eligible phase III randomized clinical trials (RCTs) evaluating the combination or sequential use of docetaxel + ADT with abiraterone, enzalutamide, apalutamide, or darolutamide. The outcomes of interest included OS, PFS, time to prostate-specific antigen (PSA) progression, grade 3–5 adverse events (AEs), and serious adverse events (SAEs). Results: Five RCTs involving 2836 patients were included in the analysis. When comparing ARSis sequential therapy to ARSis combined therapy, no significant differences were observed in OS (Hazard Ratio (HR): 1.17, 95% Confidence Interval (CI): 0.69–1.96), PFS (HR: 1.03, 95% CI: 0.47–2.22), or time to PSA progression (HR: 0.48, 95% CI: 0.03–7.69). Within the different ARSis combined regimens, the triple therapies involving enzalutamide, abiraterone, and darolutamide demonstrated comparable efficacy and safety profiles in the overall population, and their efficacy in patients with high-volume disease or low-volume disease was also similar. Conclusion: ARSis sequential therapy did not significantly differ from ARSis combined therapy in improving OS and PFS among patients with mHSPC, and thus can be considered as a viable treatment option. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Previous studies have investigated complexation and coacervation of scallop Patinopecten yessoensis male gonad hydrolysates (SMGHs) and polysaccharides influenced by pH and blending ratio. It has been found that SMGHs/polysaccharide composite shows better gel properties under strongly acidic conditions. Thus, the complexation and coacervation of SMGHs and gellan gum (GG) were investigated via turbidimetric titration at different pH values (1–12) and biopolymer blending ratios (9.5:0.5–6:4).Both pHc and pHφ1 exhibited ratio‐independent behavior with constant values at approximately pH 5.8 and pH 3.8, respectively, dividing SMGHs/GG blends into three phases named mixed polymers, soluble complexes and insoluble coacervates, respectively. Overall, SMGHs and GG exhibited synergistic gelation under neutral and acidic conditions, with the initial storage modulus (G') increasing by approximately 42.5‐, 573.7‐ and 3421‐fold and 97.7‐, 550.3‐ and 0.5‐fold, respectively, at pH 7, 5 and 3, compared with SMGHs and GG. As pH decreased from 7 to 3, the initial G' and viscosity η values of SMGHs/GG gels increased by 20.1‐ and 2.3‐fold, respectively, exhibiting the greatest increase in gel strength. Moreover, the free water in the SMGHs/GG system significantly shifted toward lower relaxation times attributed to the immobilization of the outer hydration layers. SMGHs/GG gels in the insoluble phase exhibited denser networks and rougher surfaces, supporting the enhanced rheological properties and water retention capacity of the gel.This work provides a basic foundation for the development of pH‐driven SMGHs/GG gelation by examining complexation and coacervation processes. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Objective To study the characteristics of fatigue and the correlation between fatigue and other symptoms of Parkinson's disease (PD). Methods According to Fatigue Severity Scale (FSS), 100 PD patients enrolled in this study were divided into fatigue group (FSS > 4 score, N = 58) and non- fatigue group (FSS ≤ 4 score, N = 42). Unified Parkinson's Disease Rating Scale III (UPDRS III), revised Hoehn-Yahr stage and modified Webster score were used to investigate the severity of motor symptom. Non- Motor Symptoms Scale (NMSS), Mini-Mental State Examination (MMSE), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were adopted to measure the severity of non-motor symptom. In addition, UPDRSII was used to evaluate the activities of daily living and 39-Item Parkinson's Disease Questionnaire (PDQ-39) was used to measure life quality of PD patients, respectively. Results There were 58 out of 100 PD patients having fatigue symptom, namely the occurrence rate of fatigue was 58%. The occurrence rate of daytime nap (χ² = 16.256, P = 0.000), fatigue (χ² = 84.639, P = 0.000), lack of interest (χ² = 10.705, P = 0.001), lack of passion (χ² = 9.350, P = 0.002), depression (χ² = 9.350, P = 0.002), anxiety/panic (χ² = 4.625, P = 0.032), emotional apathy (χ² = 22.032, P = 0.000), anhedonia (χ² = 18.247, P = 0.000), poor memory (χ² = 4.366, P = 0.037), urgency of urination (χ² = 5.774, P = 0.016), frequency of micturition (χ² = 5.774, P = 0.016), hard in sex life (χ² = 3.877, P = 0.049), and decreased sense of smell or taste (χ² = 5.360, P = 0.021) were significantly higher in PD patients of fatigue group than those in non-fatigue group. UPDRS III scores (t = 6.374, P = 0.000), revised Hoehn-Yahr stage (Z = - 3.345, P = 0.001), modified Webster score (t = 6.819, P = 0.000), NMSS (t = 2.923, P = 0.011), HAMD (Z = - 2.451, P = 0.014), HAMA (t = 5.417, P = 0.000), ESS (Z = - 2.116, P = 0.034), UPDRS II (Z = - 3.115, P = 0.002) and PDQ - 39 (Z = - 2.696, P = 0.007) were significantly higher in PD patients of fatigue group than those in non - fatigue group. Spearman rank correlation analysis indicated that FSS scores had high positive correlation with modified Webster score (rs = 0.622, P = 0.000) and NMSS (rs = 0.611, P = 0.000), moderate positive correlation with duration (rs = 0.582, P = 0.000), UPDRS III (rs = 0.573, P = 0.000), revised Hoehn-Yahr stage (rs = 0.542, P = 0.000), HAMD (rs = 0.505, P = 0.000), HAMA (rs = 0.477, P = 0.000), ESS (rs = 0.474, P = 0.000), PSQI (rs = 0.410, P = 0.000), UPDRS II (rs = 0.559, P = 0.000) and PDQ-39 (rs = 0.578, P = 0.000), and low negative correlation with MMSE (rs = - 0.258, P = 0.000). Conclusions The occurrence of fatigue in PD is high, which has interaction effect with other symptoms of PD, consequently affecting the life quality of PD patients. [ABSTRACT FROM AUTHOR]