Objective To analyze ethnic differences in mutations of the PIK3CA and TP53 genes among breast cancer patients from the Han, Tibetan, and Hui ethnic groups in Qinghai, China, and their associations with clinicopathological characteristics. Methods A total of 382 breast cancer tissue samples were retrospectively collected from surgical patients (Jan 2020−Dec 2022), comprising 200 Han, 93 Tibetan, and 89 Hui ethnicity. Mutations in PIK3CA (E542K, H1047R, and E545K) and TP53 (R273H and R175H) were detected by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Correlations between mutations and clinicopathological parameters were analyzed. Results Significant differences were observed in pTNM stage, lymph node metastasis, molecular subtypes, and PR status among the three ethnic groups. The overall mutation rate of PIK3CA and TP53 was 48.95%. The PIK3CA-p.E542K mutation rate in Tibetan cohort was significantly higher than those in Han and Hui cohort, whereas the detection rate of the PIK3CA-p.E545K mutation was lower in Tibetan cohort than that in Han cohort. The PIK3CA-p.E542K mutation was associated with an increased risk of lymph node metastasis. The TP53-p.R175H mutation was significantly correlated with advanced pTNM stage, vascular invasion, and triple-negative breast cancer. The PIK3CA-H1047R and E545K mutations were enriched in the luminal A subtype of breast cancer. Conclusion Considerable ethnic disparities exist in breast cancer mutation profiles in Qinghai, with the high-frequency PIK3CA-p.E542K mutation in Tibetan population potentially serving as a region-specific therapeutic target. Mutations are closely linked to tumor aggressiveness and molecular subtypes, highlighting the value of PIK3CA/TP53 mutation detection for early risk stratification and personalized treatment of breast cancer in high-altitude populations.

Clinical chemotherapy for prostate cancer is still compromised by high treatment thresholds and severe off-target toxicity of drugs. Given the limited progress in improving therapeutic outcomes and reducing toxicity with the existing toolbox, efforts to broaden the chemotherapeutic window are highly desired. Here, we discover that gossypol (GSP, a natural compound) dramatically enhances the chemosensitivity of cabazitaxel (CTX), even at previously ineffective concentrations. Based on this interesting finding, we exploit a carrier-free chemotherapeutic nano-booster for prostate cancer treatment, which is molecularly co-assembled by GSP and cabazitaxel (CTX). GSP not only readily forms nanoassembly with CTX, but also functions as a chemotherapeutic enhancer that unlocks an ultra-low-dose chemotherapeutic window. Not only that, precise dual-drug nanoassembly confers CTX a significantly larger maximum tolerable dose. As expected, the nano-booster exerts striking therapeutic benefits in mouse prostate tumor xenograft models. This study advances chemotherapeutic window expansion and self-sensitized chemotherapy toward clinical applicability.

Objective:To detect the expression of autophagy-related genes (ATGs) involved in the late stage of autophagy in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS), analyze the difference and explore its possible clinical significance.Methods:① Peripheral blood specimens and clinical data were collected from 90 AS patients (AS group) who attended the outpatient clinic of the Department of Rheumatology and Immunology of the Affiliated Hospital of North Sichuan Medical College from March 2022 to August 2023, among which 30 patients were treated with secukinumab monoclonal antibody for 24 weeks (the treatment group), and clinical data and peripheral blood specimens from 45 healthy individuals (the HC group) who had medical checkups in the Affiliated Hospital of Chuanbei Medical College during the same period were used as the control group. As the control group, the mRNA expression levels of six ATGs (ATG5, ATG7, LC3-Ⅱ, ATG4B, ATG2A, ATG10) involved in the late autophagy stage were detected in PBMCs of peripheral blood specimens by RT-qPCR, and were compared among different groups, and the measured data conformed to the normal distribution were analyzed using the paired t-test, and the abnormal distribution date were analyzed using the Wilcoxon signed-rank test. Wilcoxon signed-rank test was used for measurement data, and Spearman correlation analysis was used for correlation analysis. ② Receiver operating curve (ROC) was used to verify the difference in the expression of ATGs in the late stage of autophagy between AS group and HC group to evaluate its value in the diagnosis of AS and the inflammatory state of the disease. Results:① Compared with the HC group, ATG2A [2.00(1.10, 2.70)×10 -3, 7.50(4.60, 10.0)×10 -3, Z=-6.67, P<0.001], ATG5 [3.60 (2.30, 5.30)×10 -3, 7.20(5.50, 9.20)×10 -3, Z=-3.63, P=0.001], LC3Ⅱ[25.70(8.50, 35.00)×10 -3, 52.20(45.00, 69.10)×10 -3, Z=-5.87, P<0.001] and ATG7[5.50(3.20, 8.10)×10 -3, 8.30(5.20, 9.80)×10 -3, Z=-2.38, P=0.017] the mRNA expressions were significantly decreased in the AS group. ②ATG5 mRNA expression was negatively correlated with platelet count ( r=-0.35, P=0.008), LC3-Ⅱ was negatively correlated with estimated glomerular filtration rate ( r=-0.33, P=0.017), ATG7 was positively correlated with absolute basophil count ( r=0.33, P=0.011),ATG10 was negatively correlated with estimated glomerular filtration rate and C-reactive protein (CRP) was negatively correlated ( r=-0.30, P=0.032). ③ The area under the ROC curve (AUC) of ATG2A mRNA expression level for predicting AS was 0.910, and the sensitivity and specificity were 94.6% and 83.8% respectively. ④ After 24 weeks of treatment with secukinumab, the mRNA expression levels of ATG2A[2.00(1.20, 2.90)×10 -3, 4.90(0.10, 7.40)×10 -3, Z=-3.75, P<0.001] and LC3-Ⅱ[2.00(1.20, 2.90)×10 -3, 4.90(0.10, 7.40)×10 -3, Z=-3.75, P<0.001]were elevated in the AS patients. Conclusion:Late autophagy-related genes ATG2A, ATG5, LC3II, ATG7 may be involved in AS development.The AUC of ATG2A in AS is 0.91, suggesting that ATG2a is expected to be a biological indicator for early diagnosis of AS. Secukinumab may be involved in the regulation of autophagy by affecting the expression of late autophagy genes, but the specific mechanism needs to be further explored.

Objective:To detect the expression of autophagy-related genes (ATGs) involved in the late stage of autophagy in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS), analyze the difference and explore its possible clinical significance.Methods:① Peripheral blood specimens and clinical data were collected from 90 AS patients (AS group) who attended the outpatient clinic of the Department of Rheumatology and Immunology of the Affiliated Hospital of North Sichuan Medical College from March 2022 to August 2023, among which 30 patients were treated with secukinumab monoclonal antibody for 24 weeks (the treatment group), and clinical data and peripheral blood specimens from 45 healthy individuals (the HC group) who had medical checkups in the Affiliated Hospital of Chuanbei Medical College during the same period were used as the control group. As the control group, the mRNA expression levels of six ATGs (ATG5, ATG7, LC3-Ⅱ, ATG4B, ATG2A, ATG10) involved in the late autophagy stage were detected in PBMCs of peripheral blood specimens by RT-qPCR, and were compared among different groups, and the measured data conformed to the normal distribution were analyzed using the paired t-test, and the abnormal distribution date were analyzed using the Wilcoxon signed-rank test. Wilcoxon signed-rank test was used for measurement data, and Spearman correlation analysis was used for correlation analysis. ② Receiver operating curve (ROC) was used to verify the difference in the expression of ATGs in the late stage of autophagy between AS group and HC group to evaluate its value in the diagnosis of AS and the inflammatory state of the disease. Results:① Compared with the HC group, ATG2A [2.00(1.10, 2.70)×10 -3, 7.50(4.60, 10.0)×10 -3, Z=-6.67, P<0.001], ATG5 [3.60 (2.30, 5.30)×10 -3, 7.20(5.50, 9.20)×10 -3, Z=-3.63, P=0.001], LC3Ⅱ[25.70(8.50, 35.00)×10 -3, 52.20(45.00, 69.10)×10 -3, Z=-5.87, P<0.001] and ATG7[5.50(3.20, 8.10)×10 -3, 8.30(5.20, 9.80)×10 -3, Z=-2.38, P=0.017] the mRNA expressions were significantly decreased in the AS group. ②ATG5 mRNA expression was negatively correlated with platelet count ( r=-0.35, P=0.008), LC3-Ⅱ was negatively correlated with estimated glomerular filtration rate ( r=-0.33, P=0.017), ATG7 was positively correlated with absolute basophil count ( r=0.33, P=0.011),ATG10 was negatively correlated with estimated glomerular filtration rate and C-reactive protein (CRP) was negatively correlated ( r=-0.30, P=0.032). ③ The area under the ROC curve (AUC) of ATG2A mRNA expression level for predicting AS was 0.910, and the sensitivity and specificity were 94.6% and 83.8% respectively. ④ After 24 weeks of treatment with secukinumab, the mRNA expression levels of ATG2A[2.00(1.20, 2.90)×10 -3, 4.90(0.10, 7.40)×10 -3, Z=-3.75, P<0.001] and LC3-Ⅱ[2.00(1.20, 2.90)×10 -3, 4.90(0.10, 7.40)×10 -3, Z=-3.75, P<0.001]were elevated in the AS patients. Conclusion:Late autophagy-related genes ATG2A, ATG5, LC3II, ATG7 may be involved in AS development.The AUC of ATG2A in AS is 0.91, suggesting that ATG2a is expected to be a biological indicator for early diagnosis of AS. Secukinumab may be involved in the regulation of autophagy by affecting the expression of late autophagy genes, but the specific mechanism needs to be further explored.

Objective:To detect the expression of autophagy-associated genes (ATGs) involved in the early stage of autophagy in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and analyze the results with clinical data. To explore the association between the early stage of autophagy and AS and the clinical significance of ATGs involved in the early stage of autophagy in assessing the disease and inflammatory status of AS.Methods:①Clinical data and peripheral blood samples of 90 patients with AS (AS group) who were admitted to the Rheumatology and Immunology Department of the Affiliated Hospital of North Sichuan Medical College from March 2021 to August 2022 were collected, including 32 patients in the active stage (ASA group) and 58 patients in the stable stage (ASS group). In addition, clinical data and peripheral blood samples of 30 patients who were treated with secuchiumab for 24 weeks were also collected. The clinical data and peripheral blood samples of 45 healthy control (HC group) who underwent physical examination at the Affiliated Hospital of Sichuan Northwest Medical University at the same time served as controls for clinical data and peripheral blood specimens were used as controls. RT-qPCR was used to detect the mRNA expression levels of 8 ATGs (ATG13, ATG14, ATG17, ATG18, ATG101, Beclin1, ULK1, mTOR) involved in the early stage of autophagy in all PBMCs of peripheral blood samples, and compared between different groups. Data that follows a normal distribution is tested using the t-test, while data that does not follow a normal distribution is tested using the Wilcoxon rank sum test. Correlation analysis is performed using Spearman's rank correlation coefficient.②Receiver operating curve (ROC) was used to evaluate the value of ATGs with differential expression between AS group and HC group in detecting AS disease.Results:①Compared with HC group, the level of ATG13, ATG14, ATG17, ATG18, ATG101 and Beclin1 mRNA in AS group were significantly lower than those in HC group[ATG3:3.52(1.95, 5.09)×10 -3, 7.21(5.49, 9.16)×10 -3, Z=-5.64, P<0.001; ATG14:2.48(1.85, 3.64)×10 -3, 6.16(4.27, 7.80)×10 -3, Z=-6.44, P<0.001; ATG17: 6.45(3.29, 9.48)×10 -3, 18.52(12.30, 22.51)×10 -3, Z=-6.18, P<0.001;ATG18:2.97(1.77, 4.37)×10 -3, 4.61(3.27, 5.59)×10 -3, Z=-3.88, P<0.001; ATG101: 2.07(1.11, 3.33)×10 -3, 3.65(2.41, 5.20)×10 -3, Z=-3.87, P<0.001; Beclin1: 3.50(0.63, 6.14)×10 -3, 4.17(2.82, 7.93)×10 -3, Z=-1.82, P=0.027]. ②Comparison between ASA and ASS groups: The levels of ATG17, ATG 101 and Beclin1 mRNA in ASA group were significantly lower than those in ASS group[ATG17: 4.61(2.75, 7.85)×10 -3, 6.86(3.85, 11.28)×10 -3, Z=-2.16, P=0.030; ATG101:0.93(0.40, 1.67)×10 -3, 2.15(1.17, 3.20)×10 -3, Z=-3.94, P=0.002; Beclin1: 1.24(0.52, 3.94)×10 -3, 3.86(1.55, 5.45)×10 -3, Z=-2.26, P=0.024]. ③Spearman correlation analysis showed that the mRNA expression levels of ATG13 and Beclin1 in AS were negatively correlated with ESR and hs-CRP, respectively ( r=-0.22, P=0.038; r=-0.30, P=0.006; r=-0.34, P=0.004; r=-0.241, P=0.037), ATG18 mRNA expression ESR was positively correlated ( r=0.22, P=0.041). ④ROC curve showed that ATG13, ATG14, and ATG17 had a good ability to predict AS, and their area under the curve (AUC) was 0.821, 0.866, and 0.851, respectively. The mRNA expression levels of ATG13, ATG14, and ATG18 in AS were significantly increased after 24 weeks of secuchiumab treatment[ATG13: 3.09(0.17, 4.48)×10 -3, 3.50(3.42, 3.57)×10 -3, Z=-3.45, P=0.001; ATG14: 2.49(1.43, 4.03)×10 -3, 5.62(2.28, 6.77)×10 -3, Z=-3.01, P=0.003; ATG18: 2.91(1.61, 4.37)×10 -3, 4.53(2.91, 5.73)×10 -3, Z=-3.34, P=0.001]. Conclusion:①The different expressions of ATG13, ATG14, ATG17, ATG18, ATG101, and Beclin1 between HC and AS suggest that these 6 genes may related to the pathogenesis of AS, among which Beclin1 and ATG13 are closely related to the levels of inflammatory indicators ESR and hs-CRP in patients. It may affect the inflammatory state in AS. ②IL-17Ai may be a potential regulator of autophagy, which can play a therapeutic role by affecting the early autophagy process in AS, but the specific mechanism needs to be further explored. ③ Genes related to the early stage of autophagy are expected to be biological indicators for monitoring the occurrence of AS.

Objective:To detect the expression of autophagy-associated genes (ATGs) involved in the early stage of autophagy in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and analyze the results with clinical data. To explore the association between the early stage of autophagy and AS and the clinical significance of ATGs involved in the early stage of autophagy in assessing the disease and inflammatory status of AS.Methods:①Clinical data and peripheral blood samples of 90 patients with AS (AS group) who were admitted to the Rheumatology and Immunology Department of the Affiliated Hospital of North Sichuan Medical College from March 2021 to August 2022 were collected, including 32 patients in the active stage (ASA group) and 58 patients in the stable stage (ASS group). In addition, clinical data and peripheral blood samples of 30 patients who were treated with secuchiumab for 24 weeks were also collected. The clinical data and peripheral blood samples of 45 healthy control (HC group) who underwent physical examination at the Affiliated Hospital of Sichuan Northwest Medical University at the same time served as controls for clinical data and peripheral blood specimens were used as controls. RT-qPCR was used to detect the mRNA expression levels of 8 ATGs (ATG13, ATG14, ATG17, ATG18, ATG101, Beclin1, ULK1, mTOR) involved in the early stage of autophagy in all PBMCs of peripheral blood samples, and compared between different groups. Data that follows a normal distribution is tested using the t-test, while data that does not follow a normal distribution is tested using the Wilcoxon rank sum test. Correlation analysis is performed using Spearman's rank correlation coefficient.②Receiver operating curve (ROC) was used to evaluate the value of ATGs with differential expression between AS group and HC group in detecting AS disease.Results:①Compared with HC group, the level of ATG13, ATG14, ATG17, ATG18, ATG101 and Beclin1 mRNA in AS group were significantly lower than those in HC group[ATG3:3.52(1.95, 5.09)×10 -3, 7.21(5.49, 9.16)×10 -3, Z=-5.64, P<0.001; ATG14:2.48(1.85, 3.64)×10 -3, 6.16(4.27, 7.80)×10 -3, Z=-6.44, P<0.001; ATG17: 6.45(3.29, 9.48)×10 -3, 18.52(12.30, 22.51)×10 -3, Z=-6.18, P<0.001;ATG18:2.97(1.77, 4.37)×10 -3, 4.61(3.27, 5.59)×10 -3, Z=-3.88, P<0.001; ATG101: 2.07(1.11, 3.33)×10 -3, 3.65(2.41, 5.20)×10 -3, Z=-3.87, P<0.001; Beclin1: 3.50(0.63, 6.14)×10 -3, 4.17(2.82, 7.93)×10 -3, Z=-1.82, P=0.027]. ②Comparison between ASA and ASS groups: The levels of ATG17, ATG 101 and Beclin1 mRNA in ASA group were significantly lower than those in ASS group[ATG17: 4.61(2.75, 7.85)×10 -3, 6.86(3.85, 11.28)×10 -3, Z=-2.16, P=0.030; ATG101:0.93(0.40, 1.67)×10 -3, 2.15(1.17, 3.20)×10 -3, Z=-3.94, P=0.002; Beclin1: 1.24(0.52, 3.94)×10 -3, 3.86(1.55, 5.45)×10 -3, Z=-2.26, P=0.024]. ③Spearman correlation analysis showed that the mRNA expression levels of ATG13 and Beclin1 in AS were negatively correlated with ESR and hs-CRP, respectively ( r=-0.22, P=0.038; r=-0.30, P=0.006; r=-0.34, P=0.004; r=-0.241, P=0.037), ATG18 mRNA expression ESR was positively correlated ( r=0.22, P=0.041). ④ROC curve showed that ATG13, ATG14, and ATG17 had a good ability to predict AS, and their area under the curve (AUC) was 0.821, 0.866, and 0.851, respectively. The mRNA expression levels of ATG13, ATG14, and ATG18 in AS were significantly increased after 24 weeks of secuchiumab treatment[ATG13: 3.09(0.17, 4.48)×10 -3, 3.50(3.42, 3.57)×10 -3, Z=-3.45, P=0.001; ATG14: 2.49(1.43, 4.03)×10 -3, 5.62(2.28, 6.77)×10 -3, Z=-3.01, P=0.003; ATG18: 2.91(1.61, 4.37)×10 -3, 4.53(2.91, 5.73)×10 -3, Z=-3.34, P=0.001]. Conclusion:①The different expressions of ATG13, ATG14, ATG17, ATG18, ATG101, and Beclin1 between HC and AS suggest that these 6 genes may related to the pathogenesis of AS, among which Beclin1 and ATG13 are closely related to the levels of inflammatory indicators ESR and hs-CRP in patients. It may affect the inflammatory state in AS. ②IL-17Ai may be a potential regulator of autophagy, which can play a therapeutic role by affecting the early autophagy process in AS, but the specific mechanism needs to be further explored. ③ Genes related to the early stage of autophagy are expected to be biological indicators for monitoring the occurrence of AS.

Objective:To produce 161Tb from enriched 160Gd 2O 3 isotope-enriched target material and realize domestic production of the novel medical isotope 161Tb. Methods:The 160Gd 2O 3 isotope-enriched target material was irradiated with neutrons by the China Mianyang Research Reactor (CMRR). The no-carrier-added 161Tb product was obtained after the processes of target broken, sample dissolution, separation and purification with lanthanide (LN) resin and solution replacement with diglycolamide (DGA) column. Various key indicators such as γ spectral purity, metal impurity content, specific activity, radiochemical purity, and radioactive concentration were used to conduct the quality inspection and the control of 161Tb products. Results:161TbCl 3 of 33.4 GBq was obtained in a single time with the radioactive concentration of 16.8 GBq/ml, nuclear purity more than 99.9%, and radiochemical purity of 99.2%. Metal impurity content was met the established standards, with the specific activity of 6.02×10 17 Bq/mol. The radiochemical purities of 161Tb labeling with 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) after 0 and 72 h were 100% and 95.8% respectively. Conclusion:The preparation of no-carrier-added 161Tb by using LN resin has the advantages of high separation performance and high sample loading, which has great significance in the field of medical isotope preparation and lays a good nuclide guarantee for the research and development of domestic 161Tb-labeled drugs.

Objective:To investigate the current status of satisfaction with training program and loyalty to the university among professional postgraduate students majoring in clinical medicine, as well as the association between satisfaction with training program and loyalty to the university.Methods:The 2017 National Medical Student Satisfaction Survey Database was used. A total of 1 944 professional postgraduate students in the second or third year, as well as those with delayed graduation, from 59 postgraduate training colleges and universities who participated in clinical internship were selected. SPSS 20.0 software was used for analysis; descriptive analysis was used to describe satisfaction with training program and loyalty to the university; factor analysis was adopted to calculate comprehensive satisfaction score to reduce the number of variables; logistic regression analysis was applied to investigate the association of general information and satisfaction with training program with loyalty to the university.Results:The professional postgraduate students majoring in clinical medicine had a degree of 60.44% of loyalty to the university. Satisfaction with training program reflected low satisfaction at each link of the training program. For every 1-point increase in the comprehensive satisfaction scores of the four links of courses, research training, college support, and practice, the loyalty to the university was increased to 2.11, 1.83, 1.77, and 1.75 times as the original, respectively, of the baseline scores.Conclusion:There is still room for further improvement in the satisfaction with training program and the loyalty to the university among professional postgraduate students majoring in clinical medicine, and the satisfaction with training program is closely associated with the loyalty to the university. Colleges and universities need to take measures for courses, practice, research training, and college support, so as to improve satisfaction and thus enhance loyalty to the university.

Objectives? To describe the human resource allocation of ophthalmic nurses in China, and to compare the differences based on the ophthalmic nurse availability among different regions so as to put forward policy recommendations. Methods? We used the latest data of China Ophthalmic Competency Resource Survey in 2015 and China Population and Employment Statistics Yearbook to describe the quantity, education backgrounds and professional titles of ophthalmology nurses in different regions of China. Population-weighted quartiles of the county-level number were defined and used to analyze the differences in education backgrounds and professional titles among different regions and different levels of availability. Results? By the end of 2014, the number of ophthalmic nurses was 3.19 per 100 000. The eastern part had 30% more nurses than the western and the urban area had 285% more than the rural area. The ratio of ophthalmology doctors to ophthalmic nurses is 1∶1.13 while the eastern area had the lowest ratio. Most of the ophthalmic nurses held post-secondary diploma and only entry-level titles. The availability of ophthalmic nurses in the east China was better than any other parts. It was easier to get an ophthalmic nurse in the cities than in rural areas. And the condition got worst in western rural districts. The proportion of nurses with a bachelor's degree went higher with the increase in availability, while this trend reverted with regard to the proportion of senior titled nurses. With the same availability, the quality of human resources in western and rural areas is the worst. Conclusions? The resource allocation of ophthalmic nurses in China has gradually improved, but there are still problems such as regional inequality and large urban-rural gap. The availability analysis can show the inter-regional difference in terms of the quantity of ophthalmic nurses in a more detailed manner, such that the situations in the urban and rural areas are in extremely differentiated states; The quality of ophthalmic nurses in China needs to be further improved, and the quality difference will further aggravate the imbalance of resource allocation.

By analyzing 94 questionnaires of majors in medical imaging technology on medical ethics teaching,we found that some teaching models will help students realize the necessity of studying medical ethics and case teaching,including increasing the expansion of case teaching,selecting certain videos and short films into case teaching,expanding case-study model and case-exploration model,strengthening teachers' after-case-teaching summary to advance and further ethical themes.These models will also improve students' ability in ethical analysis and their sense of ethics,and will surely apply the theoretical principles into practice once they are interested in studying medical ethics.