Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Acute kidney injury (AKI), a life-threatening clinical syndrome, lacks effective therapeutic interventions beyond supportive care such as hemodialysis and kidney transplantation. Pathologically, excessive reactive oxygen species -mediated oxidative stress is recognized as a pivotal contributor to AKI progression, positioning reactive oxygen species scavenging as a critical therapeutic target. Emerging nanozymes, nanomaterials with enzyme-mimetic activities, have shown promise in addressing AKI by targeting renal oxidative stress. The article mainly reviewed the content of classification of nanozymes, research findings on nanozymes in treating AKI along with discussions on their mechanisms of action, as well as the current challenges and existing issues in nanozymes-based AKI therapy, to provide enhanced research perspectives for advancing nanozyme applications in the prevention and treatment of AKI.

Objective:To assess the levels and abnormal rates of trace elements and vitamins among older patients in Beijing Hospital, and to analyze the correlations between these measured indicators.Methods:This study selected 49 older individuals who underwent physical examinations at Beijing Hospital between May 2021 and March 2024.The participants were divided into two age groups: 60-79 years old(23 cases)and 80-100 years old(26 cases). Levels' differences of trace elements and vitamins between the two age groups were analyzed.Pearson correlation analysis was used to investigate the correlations among the tested indicators, and multivariate analysis was conducted using a generalized linear regression model.Results:Among the 49 older individuals, the overall abnormal rate for trace element test results was 8.16%(4 cases), with 2 cases of iron(Fe)deficiency(4.08%)and 2 cases of calcium(Ca)deficiency(4.08%). The overall abnormal rate for vitamin test results was 24.49%(12 cases), which included 5 cases of vitamin B2 deficiency(10.20%), 1 case of vitamin C deficiency(2.04%), and 6 cases of vitamin D deficiency(12.24%). Statistically significant differences were observed between the two age groups in zinc(Zn)and vitamin C levels( t=2.84, 2.83; P=0.007, 0.007). Pearson correlation analysis revealed correlations among 19 pairs of indicators.The top five correlations were between plumbum(Pb)and cadmium(Cd)( r=0.769, P<0.001), Fe and manganese(Mn)( r=0.685, P<0.001), Ca and magnesium(Mg)( r=0.677, P<0.001), vitamin B12 and vitamin C( r=0.455, P=0.001), and vitamin B9 and vitamin D( r=0.422, P=0.003), respectively.The results of the multivariate analysis indicated that, after adjusting for the effects of age group and gender, statistical differences in correlations remained among the remaining trace elements and vitamins, except for those between vitamin B1 and vitamin B12, vitamin B1 and vitamin C, and vitamin A and vitamin D (all P<0.05). Conclusions:The deficiency rates of trace elements and vitamins remain notably high among older patients in our hospital, underscoring the necessity for enhanced nutritional supplementation and regular monitoring of trace element and vitamin levels within this population.Furthermore, a correlation exists between trace elements and vitamins, which offers valuable insights for the diagnosis and treatment of related diseases.

Objective:To compare the advantages and disadvantages and training costs of different training methods for microsurgical vascular anastomosis, and to provide a basis for establishing a systematic training model and improving surgeons microsurgical skills and clinical competence.Methods:Doctors came from various primary hospitals and exchange groups from foreign hospitals to China, and several groups of data statistics from 2018-2023 were randomly selected for this study. The microsurgical vascular anastomosis training lasted 10 days, including 1 day of theoretical study and 9 days of practical training. A total of 48 doctors were equally divided into group A (one-person operation), group B (two-person cooperation), and group C (two-person cooperation in the first four days and one-person operation in the last five days). The differences in anastomosis time and number of anastomoses between the groups were analysed by one-way ANOVA using the software GraphPad Prism 8.3.0, with P<0.05 indicating that there were statistically significant differences in the variable data. The cost of the three training methods was investigated, and a questionnaire survey of the trainees was conducted. Results:For all the three groups, the speed of anastomosis and the number of anastomoses increased with the course of training. The duration of single-vessel anastomosis was significantly different between groups A and B as well as between groups A and C at all time points except on day 1 (A1 d vs. B1 d, P=0.335; A1 d vs. C1 d, P=0.064; P<0.05 for all the other time points); groups B and C showed no significant differences on day 1 ( P=0.196) and day 3 ( P=0.115) but had significant differences on days 5, 7, and 9 (all P<0.05) in the duration of anastomosis. The number of anastomoses was not significantly different between A1 d and B1 d ( P=0.081), between A3 d and B3 d ( P=0.160), between B1 d and C1 d ( P=0.695), between B3 d and C3 d ( P=0.520), and between A1 d and C1 d ( P=0.123), with significant differences at the other time points (all P<0.05). The training costs were group A > group C > group B. The training questionnaire showed that the proportion of trainees who applied this technique in their daily work was 100.00% (48/48), the proportion of those who wished to participate in the training of this technique occasionally was 100.00% (48/48), the proportion of participants whose institutions had no relevant training conditions was 37.50% (18/48), the proportion of those whose institutions lacked necessary instruments and equipment was 35.42% (17/48), the proportion of those who had difficulties in access to laboratory animals was 68.75% (33/48), and the proportion of inability to carry out relevant training due to the lack of animal experimentation techniques such as anesthesia, preservation, and euthanasia was 91.67% (44/48), indicating that there is a great need for microsurgical vascular anastomosis training. Conclusions:The three training modes have their own advantages and disadvantages. The A mode is suitable for small-scale training. The B mode is suitable for training with adequate funds, a large number of personnel, and a high use frequency. The C mode is the best choice for microsurgical vascular anastomosis training, in which trainees can not only practice the whole vascular anastomosis process but also cooperative skills for anastomosis.

Objective:To compare the advantages and disadvantages and training costs of different training methods for microsurgical vascular anastomosis, and to provide a basis for establishing a systematic training model and improving surgeons microsurgical skills and clinical competence.Methods:Doctors came from various primary hospitals and exchange groups from foreign hospitals to China, and several groups of data statistics from 2018-2023 were randomly selected for this study. The microsurgical vascular anastomosis training lasted 10 days, including 1 day of theoretical study and 9 days of practical training. A total of 48 doctors were equally divided into group A (one-person operation), group B (two-person cooperation), and group C (two-person cooperation in the first four days and one-person operation in the last five days). The differences in anastomosis time and number of anastomoses between the groups were analysed by one-way ANOVA using the software GraphPad Prism 8.3.0, with P<0.05 indicating that there were statistically significant differences in the variable data. The cost of the three training methods was investigated, and a questionnaire survey of the trainees was conducted. Results:For all the three groups, the speed of anastomosis and the number of anastomoses increased with the course of training. The duration of single-vessel anastomosis was significantly different between groups A and B as well as between groups A and C at all time points except on day 1 (A1 d vs. B1 d, P=0.335; A1 d vs. C1 d, P=0.064; P<0.05 for all the other time points); groups B and C showed no significant differences on day 1 ( P=0.196) and day 3 ( P=0.115) but had significant differences on days 5, 7, and 9 (all P<0.05) in the duration of anastomosis. The number of anastomoses was not significantly different between A1 d and B1 d ( P=0.081), between A3 d and B3 d ( P=0.160), between B1 d and C1 d ( P=0.695), between B3 d and C3 d ( P=0.520), and between A1 d and C1 d ( P=0.123), with significant differences at the other time points (all P<0.05). The training costs were group A > group C > group B. The training questionnaire showed that the proportion of trainees who applied this technique in their daily work was 100.00% (48/48), the proportion of those who wished to participate in the training of this technique occasionally was 100.00% (48/48), the proportion of participants whose institutions had no relevant training conditions was 37.50% (18/48), the proportion of those whose institutions lacked necessary instruments and equipment was 35.42% (17/48), the proportion of those who had difficulties in access to laboratory animals was 68.75% (33/48), and the proportion of inability to carry out relevant training due to the lack of animal experimentation techniques such as anesthesia, preservation, and euthanasia was 91.67% (44/48), indicating that there is a great need for microsurgical vascular anastomosis training. Conclusions:The three training modes have their own advantages and disadvantages. The A mode is suitable for small-scale training. The B mode is suitable for training with adequate funds, a large number of personnel, and a high use frequency. The C mode is the best choice for microsurgical vascular anastomosis training, in which trainees can not only practice the whole vascular anastomosis process but also cooperative skills for anastomosis.

Objective:To assess the levels and abnormal rates of trace elements and vitamins among older patients in Beijing Hospital, and to analyze the correlations between these measured indicators.Methods:This study selected 49 older individuals who underwent physical examinations at Beijing Hospital between May 2021 and March 2024.The participants were divided into two age groups: 60-79 years old(23 cases)and 80-100 years old(26 cases). Levels' differences of trace elements and vitamins between the two age groups were analyzed.Pearson correlation analysis was used to investigate the correlations among the tested indicators, and multivariate analysis was conducted using a generalized linear regression model.Results:Among the 49 older individuals, the overall abnormal rate for trace element test results was 8.16%(4 cases), with 2 cases of iron(Fe)deficiency(4.08%)and 2 cases of calcium(Ca)deficiency(4.08%). The overall abnormal rate for vitamin test results was 24.49%(12 cases), which included 5 cases of vitamin B2 deficiency(10.20%), 1 case of vitamin C deficiency(2.04%), and 6 cases of vitamin D deficiency(12.24%). Statistically significant differences were observed between the two age groups in zinc(Zn)and vitamin C levels( t=2.84, 2.83; P=0.007, 0.007). Pearson correlation analysis revealed correlations among 19 pairs of indicators.The top five correlations were between plumbum(Pb)and cadmium(Cd)( r=0.769, P<0.001), Fe and manganese(Mn)( r=0.685, P<0.001), Ca and magnesium(Mg)( r=0.677, P<0.001), vitamin B12 and vitamin C( r=0.455, P=0.001), and vitamin B9 and vitamin D( r=0.422, P=0.003), respectively.The results of the multivariate analysis indicated that, after adjusting for the effects of age group and gender, statistical differences in correlations remained among the remaining trace elements and vitamins, except for those between vitamin B1 and vitamin B12, vitamin B1 and vitamin C, and vitamin A and vitamin D (all P<0.05). Conclusions:The deficiency rates of trace elements and vitamins remain notably high among older patients in our hospital, underscoring the necessity for enhanced nutritional supplementation and regular monitoring of trace element and vitamin levels within this population.Furthermore, a correlation exists between trace elements and vitamins, which offers valuable insights for the diagnosis and treatment of related diseases.

Acute kidney injury (AKI), a life-threatening clinical syndrome, lacks effective therapeutic interventions beyond supportive care such as hemodialysis and kidney transplantation. Pathologically, excessive reactive oxygen species -mediated oxidative stress is recognized as a pivotal contributor to AKI progression, positioning reactive oxygen species scavenging as a critical therapeutic target. Emerging nanozymes, nanomaterials with enzyme-mimetic activities, have shown promise in addressing AKI by targeting renal oxidative stress. The article mainly reviewed the content of classification of nanozymes, research findings on nanozymes in treating AKI along with discussions on their mechanisms of action, as well as the current challenges and existing issues in nanozymes-based AKI therapy, to provide enhanced research perspectives for advancing nanozyme applications in the prevention and treatment of AKI.

Background and objective Pembrolizumab(PEM)has been shown to be effective in clinical trials for the treatment of advanced non-small cell lung cancer(NSCLC),but clinical trials were based on cohorts of patients selected on specific criteria,and whether the findings are consistent with real-world patients is debatable.The aim of this study is to evaluate the efficacy and safety of PEM in the treatment of advanced NSCLC based on real-world data.Methods A retro-spective collection of real-world data from patients with advanced NSCLC receiving PEM was conducted.Propensity score matching was used to eliminate inter-group differences and assess the efficacy and safety of PEM compared to chemotherapy.Results Among 450 matched patients,the incidence rates of any-grade adverse events were 79.87％in the PEM group and86.71％inthe chemotherapy group,while the incidence rates of grade＞3 adverse events were 4.03％and 7.31％,respectively.The objective response rates were 48.63％for PEM and 36.00％for chemotherapy(P=0.011).The median progression-free survival was 15.5 months for PEM and 8.8 months for chemotherapy(P＜0.001),and the median overall survival was not reached for PEM and 26.2 months for chemotherapy(P＜0.001).Conclusion PEM treatment for advanced NSCLC demonstrates favorable survival outcomes and acceptable safety in real-world clinical practice.

Objective To understand and summarize the clinicopathological characteristics and differential diagnosis of lymphoepithelial sialadenitis(LESA)-like thymic hyperplasia.Methods The clinicopathological data of patients with LESA-like thymic hyperplasia diagnosed in our hospital from October 1,2019 to September 1,2023 were collected,and the related literatures on their epidemiological characteristics,clinicopathological features,treatments and prognosis were reviewed.Results There were 2 female patients with LESA-like thymic hyperplasia included,at an onset age of 51 and 52 years,respectively.Imaging examination revealed an anterior mediastinal mass in both patients,with the largest diameter of 7.5 and 12.0 cm,respectively.Microscopic morphology and immunophenotype analysis showed there were florid lymphoid follicles with germinal centers.Reticular or nested thymic epithelial,thymic corpuscles and lymphoepithelial lesions without dysplasia were seen in the interfollicular areas as well.Focal cystic changes,cholesterol crystals and the formation of cholesterol granuloma were observed.Our results were similar to the pathological morphology and immunohistochemical phenotype of 46 cases with LESA-like thymic hyperplasia reported in the literature.They had favorable prognosis,except 5 patients progressed to lymphoma.Conclusion LESA-like thymic hyperplasia is a benign disease with unique morphological characteristics and of favorable prognosis.But rare patients can progress to lymphoma,therefore regular and close follow-up is still required.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone