BACKGROUND:Premature birth is a major global health problem associated with high mortality and morbidity.White matter injury is the most common brain injury in preterm infants.Salvia miltiorrhiza is a traditional herbal plant that is commonly used to treat cardiovascular and cerebrovascular diseases in Asian countries. OBJECTIVE:To investigate the therapeutic effect of Salvia miltiorrhiza on white matter injury in preterm infants. METHODS:Eighteen neonatal male Sprague-Dawley rats at 3-day gestational age were selected and randomized into normal group,white matter injury group,and Salvia miltiorrhiza group.Animal models of preterm white matter injury were established by permanent ligation of the right common carotid artery in the latter two groups.Rats in the Salvia miltiorrhiza group were given intraperitoneal injection of Salvia miltiorrhiza(5 mg/kg·d)for 7 consecutive days.Normal group and white matter injury group were given the same volume of PBS for intervention.On the 14th day after modeling,the rats were sacrificed.Brains were pathologically observed by hematoxylin-eosin staining under microscope,and the expression levels of myelin basic protein and CC1 in brain tissue were visualized using immunofluorescence.Furthermore,liquid chromatography-tandem mass spectrometry was used to analyze possible pathways for the action of Salvia miltiorrhiza. RESULTS AND CONCLUSION:In the white matter injury group,the structure of the corpus callosum was irregular and the cells appeared swollen and necrotic.In addition,induction of white matter injury resulted in significantly reduced myelin formation,with irregular and loosely arranged nerve fibers and significantly decreased myelin sheaths.Interestingly,white matter injury rats treated with Salvia miltiorrhiza had reduced cellular swelling,reduced lesions,and increased myelin sheaths.The expression of myelin basic protein was closely related to myelin formation,and CC1 was a marker of myelin oligodendrocytes.Salvia miltiorrhiza significantly up-regulated the expressions of myelin basic protein and CC1 in white matter injury rats(P＜0.000 1),indicating that Salvia miltiorrhiza alleviated white matter injury.Liquid chromatography-tandem mass spectrometry analysis showed that the therapeutic effect of Salvia miltiorrhiza in the rat model of white matter injury was closely related to the regulation of complement and coagulation cascades.To conclude,Salvia miltiorrhiza may be a potential therapeutic agent for treating preterm white matter injury.

Objective:To study the structure of medical students' professional psychological quality and to compile a questionnaire.Methods:Based on the grounded theory research and semi-structured interviews, the concept and structure of medical students' professional psychological quality were constructed, and the questionnaire of professional psychological quality of medical students with qualified reliability and validity was compiled. The medical students from multiple universities in Sichuan were tested by convenient sampling. A total of 300 valid questionnaires were collected for item analysis, 400 for correlation analysis and exploratory factor analysis, and 400 for confirmatory factor analysis and reliability analysis. SPSS 25.0 was used to perform correlation analysis, exploratory factor analysis, and reliability analysis, and AMOS 26.0 was used to make confirmatory factor analysis.Results:The questionnaire of medical students' professional psychological quality consisted of three subscales: professional psychological personality, professional psychological ability and professional identity, consisting of 13 secondary factors and 61 items. The total Cronbach's α=0.947, the internal consistency coefficients of the total questionnaire and the three subscales were from 0.845 to 0.947, and the correlation coefficients between the three subscales and the total questionnaire were from 0.850 to 0.869. The three factor model fitted well (GFI=0.945, AGFI=0.906, NFI=0.936, RFI=0.906, IFI=0.957, TLI=0.935, RMSEA=0.070). Conclusion:Professional psychological personality, professional psychological ability, and professional identity are the core structures of medical students' professional psychological quality. Medical students' professional psychological quality questionnaire has good content validity, structural validity and internal consistency reliability, which can be used as an effective tool to evaluate the professional psychological quality of medical students.

Objective:To analyze germline genetic testing in Chinese high-to very-high-risk non-metastatic prostate cancer patients.Methods:This study included 249 Chinese patients with high- to very-high-risk non-metastatic prostate cancer for germline genetic testing, in Fudan University Shanghai Cancer Center, West China Hospital and Cancer Center of Sun Yat-sen University, from January 2018 to December 2022. High risk and very-high risk are termed according to National Comprehensive Cancer Network (NCCN) Prostate Cancer Guideline (2022 V1). The mean age of the patients was (66.7±9.2) years old and median PSA level was 28.50 (ranging 2.43 - 1481.11) ng/ml. Within these 249 patients, 84 (33.7%) were T 1-2, 98 (39.3%) were T 3-4, while 67 (26.9%) were unclear in T stage. Additionally, 51 patients (20.5%) were classified into International Society of Urological Pathology(ISUP) grade group 1-3 group and 198 patients (79.5%) were in ISUP 4-5 group. Focusing on 16 genetic susceptibility genes for prostate cancer, we interpret the germline genetic testing data in accordance with the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guideline, clarify the germline pathogenic mutation rate and elucidate the clinicopathological characteristics of germline pathogenic mutation carriers. Results:Among Chinese high-to very-high-risk non-metastatic prostate cancer patients, 7.2% (18/249) had germline pathogenic mutations. Patients with mutations had a significantly higher proportion of first-degree relatives with a history of malignancy than those without mutations (50% vs. 13%, P<0.001), but there was no difference in age of onset [(68.2±9.3)years vs. (66.6±9.2) years], PSA level (median: 40.68 ng/ml vs. 28.00 ng/ml), T stage [T 3-4: 38.9%(7/18)vs. 39.4%(91/231)] and ISUP grade [group 4-5: 88.9%(16/18) vs. 78.8%(182/231)]. Germline pathogenic mutations were observed in BRCA2 (7 patients, 38.9%), MSH2 (3 patients, 16.7%), PALB2 (2 patients, 11.1%), ATM (2 patients, 11.1%), RAD51C (1 patient, 5.6%), PMS2 (1 patient, 5.6%), MSH6 (1 patient, 5.6%) and HOXB13 (1 patient, 5.6%). By comparing with normal controls of East-Asian population, germline pathogenic mutations in BRCA2 ( OR=11.1, 95% CI 4.8-25.6, P<0.001) and MSH2 ( OR= 43.5, 95% CI 8.5-200.0, P<0.001) can significantly increase the risk of developing high- to very-high-risk prostate cancer in Chinese males. Conclusions:This study identified a germline pathogenic mutation rate of 7.2% in 249 Chinese patients with high- or very-high-risk non-metastatic prostate cancer. Carrying germline BRCA2 or MSH2 pathogenic mutations can significantly increase the risk of high- or very-high-risk prostate cancer in Chinese men.

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.

Natural products are essential sources of antitumor drugs. One such molecule, β-elemene, is a potent antitumor compound extracted from Curcuma wenyujin. In the present investigation, a series of novel 13,14-disubstituted nitric oxide (NO)-donor β-elemene derivatives were designed, with β-elemene as the foundational compound, and subsequently synthesized to evaluate their therapeutic potential against leukemia. Notably, the derivative labeled as compound 13d demonstrated a potent anti-proliferative activity against the K562 cell line, with a high NO release. In vivo studies indicated that compound 13d could effectively inhibit tumor growth, exhibiting no discernible toxic manifestations. Specifically, a significant tumor growth inhibition rate of 62.9% was observed in the K562 xenograft tumor mouse model. The accumulated data propound the potential therapeutic application of compound 13d in the management of leukemia.
Humans ; Mice ; Animals ; Cell Line, Tumor ; Nitric Oxide Donors/pharmacology* ; Sesquiterpenes/pharmacology* ; Leukemia/drug therapy* ; Biological Assay ; Cell Proliferation