Objective:To observe the efficacy and safety of radium-223 in metastatic castration resistant prostate cancer (mCRPC) with bone metastasis.Methods:The clinical data of 48 patients with mCRPC treated with radium-223(55 kBq/kg, once every 4 weeks, planned to use for 6 cycles)from February 2021 to May 2022 were analyzed retrospectively. All patients had symptomatic bone metastasis without visceral metastasis, which the number of bone metastasis was more than one site.They were all classified as IVb stage. The average age was 70.5 (ranging 49-90) years. The median PSA was 44.70(ranging 0.15-1 864.00) ng/ml. The median ALP was 162 (ranging 43-1 589) U/L. The median time from mCRPC diagnosis to radium-223 use was 10 (ranging 3-47) months. 9, 18 and 11 patients had received first-line, second-line and third-line treatment for mCRPC before enrollment respectively, 10 patients had received at least fourth-line treatment. 38 (79.1%), 31 (64.5%), 30 (62.5%) and 7 (14.6%) patients had used abiraterone, enzalutamide, docetaxel and olaparib before enrollment. The probability of PSA level decrease >30%, ALP level decrease >30%, symptom improvement rate, median overall survival (OS), as well as the occurrence of treatment-related adverse reactions and the reasons for withdraw treatment were analyzed.Results:The median follow-up time was 8 (ranging 1-16) months. 11 patients completed all 6 courses of treatment. The median number of completed courses was 4 (ranging 1-6). 27 patients (56.2%) received radium-223 and bone protection drugs (Bisphosphate/ Denosumab). PSA decreased by >30% was recorded in 10 patients (20.8%) and ALP decreased by >30% was recorded in 25 patients (52.1%). 23 cases (47.9%) reported bone pain relief during treatment. Among the 9 patients who had received first-line of mCRPC previously, 6 cases (66%) had relief of bone pain symptoms, and 4 cases (44%) had a decrease of PSA >30%. Among the 18 patients who had previously received second-line mCRPC treatment, 11 cases (61%) had relief of bone pain symptoms, and 4 cases (22%) had a decrease of PSA >30%. Among the 21 patients who had received third-line or more mCRPC treatment in the past, 6 (28.5%) had symptom relief, and 2 (9.5%) had PSA decrease >30%. The median overall survival (OS) was not reached, and the OS was estimated to be 12.5 months using the Kaplan-Meier method. The most common hematological adverse effects were thrombocytopenia (15 cases, 31.2%; grade 3 in 6 cases and grade 4 in 0), followed by leucopenia (11 cases, 22.9%; grade 3 in 4 cases and grade 4 in 1 case) and anemia (8 cases, 16.7%; grade 3 in 3 cases and grade 4 in 0). Non-hematological adverse reactions included fever in 1 case (2.1%), constipation in 4 cases (8.3%), nausea and vomiting in 10 cases (20.8%), diarrhea in 7 cases (14.6%), dizziness in 1 case (2.1%) and fatigue in 11 cases (22.9%). Seven cases were discontinued due to intolerable adverse reactions (median 2 courses), 14 cases were discontinued due to disease progression or death (median 2 courses), and 5 cases were discontinued due to other reasons (median 1 course).Conclusions:Radium-223 has a good performance in symptom control for mCRPC patients who have previously received first-line or second-line therapy. Due to the high incidence of hematological adverse reactions, more attention should be paid to the changes of hemogram during the treatment, and timely treatment should be carried out to improve the drug tolerance of patients.

Objective:To investigate the effects of different intensity of lighting on normal refractive development and form deprivation myopia (FDM) in guinea pigs.Methods:A total of 108 healthy 3-week-old guinea pigs were divided into normal refractive development guinea pigs ( n=54) and FDM guinea pigs ( n=54). FDM models were prepared in FDM animals by occlusion of the left eyes using an opaque mask, and the bilateral eyes were open in the normal refractive development guinea pigs.The guinea pigs were randomized to low (20 lx), normal(300 lx), and high intensity-lighting (5 000 lx) groups with a 12-hour light/12-hour dark cycle for 6 consecutive weeks under LED light.The ocular biometry was performed in a two-week interval.Axial length (AL) and dilated diopter were measured by A-scan ultrasonography and retinoscopy, respectively, and were compared after different lighting durations, and the change trends of them in normal refractive development and FDM guinea pigs were evaluated. Results:The AL values were not significantly different among low, normal and high intensity-lighting groups ( Fgroup=0.365, P=0.697), and the AL was gradually prolonged over the lighting duration ( Ftime=353.750, P<0.001). The diopters showed a statistically significant difference among different intensity-lighting groups ( Fgroup=3.576, P=0.034). The diopter in high intensity-lighting for 4 weeks was (+ 2.75±2.15) D, which was significantly higher than (0.41±3.07) D in the normal refrective development guinea pigs ( P<0.001). In the FDM guinea pigs, both AL and diopter were not significantly different among low, normal and high intensity-lighting groups ( Fgroup=0.105, P=0.900; Fgroup=0.973, P=0.387), and significant differences were seen in AL and diopter among three groups ( Ftime=408.302, 27.407; both at P<0.001). The diopter in FDM eyes of low intensity-lighting for 2 weeks was (+ 2.35±1.95) D, which was higher than (+ 1.90±0.97) D before lighting, with no statistically significant difference between them ( P>0.05). The AL was shortest and the AL change was smallest in normal refractive development guinea pigs of high intensity-lighting group.The diopter change in FDM guinea pigs of the low intensity-lighting group was significantly smaller than that in the normal intensity-lighting group ( P<0.001), with a transient hyperopia drift. Conclusions:The 5 000 lx lighting can slow down the development toward myopia in the normal refractive development eyes, and 20 lx lighting tends to delay the progression FDM eyes with a hyperopic shift after lighting for 2 weeks.