ObjectiveTo construct an interleukin-9 （Il9） gene knockout mouse model on a C57BL/6N background， establish a reliable genotyping method， and provide a standardized animal model for investigating Il9-related immune mechanisms and diseases. MethodsIl9 knockout mouse strain （C57BL/6N-Il9^em1Cya） was generated using conventional gene knockout technology. The method for DNA extraction from mouse tails was optimized to ensure template quality. Two sets of specific primers （F1/R1 and F1/R2） were designed to amplify target fragments by PCR， and mouse genotypes were determined by agarose gel electrophoresis. Specifically， primer pair F1/R1 targeted the knockout sequence with an expected product of 465 bp， while F1/R2 targeted the wild-type sequence with an expected product of 703 bp. Subsequently， Western blot was performed to verify the knockout efficiency of Il9 in primary immune cells and key organs of the offspring mice， and flow cytometry was used to assess the effects of Il9 deficiency on the function of the immune system in major immune cell populations. ResultsIl9 knockout mice were successfully bred and genotyped. PCR identification showed that homozygous mice （-/-） exhibited only a 465 bp band， wild-type mice （+/+） displayed only a 703 bp band， and heterozygous mice （+/-） showed both bands simultaneously. Meanwhile， Western blot analysis revealed significantly decreased IL-9 expression in various organs of the offspring mice （P<0.001）. Flow cytometric results demonstrated that Il9 deficiency exerted no obvious effects on the proportions of peripheral blood lymphocytes， splenic lymphocytes， and peritoneal macrophages. ConclusionAn Il9 gene knockout mouse model on a C57BL/6N background is successfully constructed. The established PCR genotyping system is highly efficient and accurate， which can effectively distinguish mice of different genotypes. This model provides a stable and reliable experimental basis for subsequent functional studies of Il9 and exploration of the mechanisms underlying Il9-related diseases.

ObjectiveTo construct a chimeric antigen receptor macrophage （CAR-M） targeting interleukin-13 receptor α （IL-13Rα） and intracellular domain integration， which can double activate the signal adaptor protein OX40L of macrophages and T cells. MethodsThe CAR molecule targeting IL-13Rα （IL-13Rα-OX40L-CAR） with OX40L as the intracellular signal domain was designed and synthesized， and it was cloned into the adenovirus expression vector. After THP-1 cells were induced to differentiate into macrophages （THP-1-M） by phorbol ester， the cells were infected with recombinant adenovirus to construct THP-1 macrophages stably expressing green fluorescent protein （GFP） labeled anti-IL-13RαCAR. The expression efficiency of CAR molecules was monitored by flow cytometry. The empty vector group was used as the negative control， the CD3ζ group was used as the positive control， and the CD3ζ-OX40L group was used as the experimental group. The phagocytic function of macrophages in each group on IL-13Rα high expression glioma cells （U251） and low expression glioma cells （T98G） was detected by in vitro co-culture experiments. ResultsCAR adenovirus was efficiently transfected into THP-1-M to obtain anti-IL-13RαCAR-M. After co-cultured with glioma cells with different expression levels of IL-13Rα， the results of flow cytometry showed that there was no significant difference among the three groups for T98G cells with low expression of IL-13Rα. After co-culture with U251 cells with high expression of IL-13Rα， the CD3ζ group showed enhanced phagocytosis compared with the empty vector group （P<0.05）. Compared with the CD3ζ group， the phagocytosis ability of the CD3ζ-OX40L group was further enhanced （P<0.05）. ConclusionAnti-IL13Rα- OX40L-CAR-M is successfully constructed by constructing IL-13Rα-OX40L-CAR adenovirus and transfecting PMA-induced differentiated THP-1-M. It can engulf glioma cells with high expression of IL-13Rα by specific targeting， and shows activation of intracellular domain superior to traditional CD3ζ.

BACKGROUND: Approximately 40% of individuals with diabetes worldwide are at risk of developing diabetic kidney disease (DKD), which is not only the leading cause of kidney failure, but also significantly increases the risk of cardiovascular disease, causing significant societal health and financial burdens. This study aimed to describe the burden of DKD and explore its cross-country epidemiological status, predict development trends, and assess its risk factors and sociodemographic transitions. METHODS: Based on the Global Burden of Diseases (GBD) Study 2021, data on DKD due to type 1 diabetes (DKD-T1DM) and type 2 diabetes (DKD-T2DM) were analyzed by sex, age, year, and location. Numbers and age-standardized rates were used to compare the disease burden between DKD-T1DM and DKD-T2DM among locations. Decomposition analysis was used to assess the potential drivers. Locally weighted scatter plot smoothing and Frontier analysis were used to estimate sociodemographic transitions of DKD disability-adjusted life years (DALYs). RESULTS: The DALYs due to DKD increased markedly from 1990 to 2021, with a 74.0% (from 2,227,518 to 3,875,628) and 173.6% (from 4,122,919 to 11,278,935) increase for DKD-T1DM and DKD-T2DM, respectively. In 2030, the estimated DALYs for DKD-T1DM surpassed 4.4 million, with that of DKD-T2DM exceeding 14.6 million. Notably, middle-sociodemographic index (SDI) quintile was responsible for the most significant DALYs. Decomposition analysis revealed that population growth and aging were major drivers for the increased DKD DALYs in most regions. Interestingly, the most pronounced effect of positive DALYs change from 1990 to 2021 was presented in high-SDI quintile, while in low-SDI quintile, DALYs for DKD-T1DM and DKD-T2DM presented a decreasing trend over the past years. Frontiers analysis revealed that there was a negative association between SDI quintiles and age-standardized DALY rates (ASDRs) in DKD-T1DM and DKD-T2DM. Countries with middle-SDI shouldered disproportionately high DKD burden. Kidney dysfunction (nearly 100.0% for DKD-T1DM and DKD-T2DM), high fasting plasma glucose (70.8% for DKD-T1DM and 87.4% for DKD-T2DM), and non-optimal temperatures (low and high, 5.0% for DKD-T1DM and 5.1% for DKD-T2DM) were common risk factors for age-standardized DALYs in T1DM-DKD and T2DM-DKD. There were other specific risk factors for DKD-T2DM such as high body mass index (38.2%), high systolic blood pressure (10.2%), dietary risks (17.8%), low physical activity (6.2%), lead exposure (1.2%), and other environmental risks. CONCLUSIONS DKD markedly increased and varied significantly across regions, contributing to a substantial disease burden, especially in middle-SDI countries. The rise in DKD is primarily driven by population growth, aging, and key risk factors such as high fasting plasma glucose and kidney dysfunction, with projections suggesting continued escalation of the burden by 2030.
Humans ; Global Burden of Disease ; Risk Factors ; Male ; Female ; Disability-Adjusted Life Years ; Diabetic Nephropathies/epidemiology* ; Middle Aged ; Diabetes Mellitus, Type 2/epidemiology* ; Adult ; Diabetes Mellitus, Type 1/complications* ; Aged ; Adolescent ; Young Adult ; Quality-Adjusted Life Years

Intensive care unit acquired weakness(ICU-AW)is common in clinical practice,especially muscle weakness and muscle dysfunction caused by delayed weaning from mechanical ventilation,which requires timely and effective imaging evaluation.Ultrasound,as a non-radiation,non-invasive,real-time and repeatable imaging technology,can serve as a preferred method for assessing muscle structure and function,and has important clinical value in the diagnosis and monitoring of ICU-AW.This review summarizes the clinical application and research progress of ultrasound examination in the non-invasive quantitative evaluation of ICU-AW.

Objective: To constructCSF1R+/-mice and to analyze their genotypes, so as to provide animal model basis for disease pathological mechanism and drug target. Methods : A linearized targeting vector was designed according to Cre/Loxp system. A Loxp site was inserted upstream of the 5th exon of theCSF1Rgene, and a neomycin resistance box with Loxp sites on both sides was inserted downstream of the 5th exon. The linearized targeting vector was electroporated into embryonic stem cells. The correctly targeted embryonic stem cells were injected into the blastocysts of C57BL/6J mice to obtain chimeric mice, which were bred with Zp3-Cre mice. The newborn mice were numbered 9-14 days after birth and their tails were cut. The DNA of the mice was extracted, and the genotype of the mice was identified by polymerase chain reaction and agarose gel electrophoresis. The expression of CSF1R in mouse macrophages was detected by flow cytometry. The expression of CSF1R in mouse tissues was detected by Western blot. Results: The results of agarose gel electrophoresis showed that 453 bp bands were amplified in wild type mice, and 453 bp and 650 bp bands were amplified in heterozygous mice. The results of flow cytometry showed that the expression of CSF1R in peritoneal macrophages and bone marrow-derived macrophages of CSF1R heterozygous mice was lower than that of WT group(P<0.05). The results of Western blot showed that the expression of CSF1R in spleen, kidney and brain tissue of CSF1R heterozygous group was lower than that of WT group(P<0.05). Conclusion CSF1R+/-mice are successfully constructed, reproduced and identified, which provides an animal model basis for further revealing the potential mechanism of CSF1R in immune regulation.

Objective:To explore the effect of EAERI (E: environment; A: accompany; E: emotion; R: respect; I: information) support strategies in the application of nurse second victims in restoring the passage of a patient safety incident, and to provide support to nurse second victims experiencing a safety incident in restoring the incident and mitigating secondary victimization from the incident.Methods:The method of historical comparison was adopted. A convenience sampling method was used to select nurses who experienced patient safety events in Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences) from January 2023 to February 2024 as the study subjects, which were divided into observation group and control group by the historical control grouping method. The observation group used the EAERI support strategy for patient safety incident reduction, and the control group used the conventional reduction method. The second victims of the nurses in both groups were assessed for their level of harm and support in the patient safety incident using the Second Victim Experience and Support Tool before and after the event reduction, respectively.Results:A total of 124 second victims completed the study. There were 63 cases in the control group, including 13 males and 50 females, with an age of (30.24 ± 4.91) years old. There were 20 males and 41 females in the observation group, with an age of (30.85 ± 5.50) years old. Before the restoration event, there was no significant differences in the total scores of victim experience and support, the degree of injury and the degree of support between the two groups (all P>0.05). The total scores of victim experience and support, the degree of injury and the degree of support were (89.35 ± 10.69), (44.57 ± 6.19), (44.78 ± 9.40) points in the control group, and (64.13 ± 9.36), (33.56 ± 8.84), (30.56 ± 3.17) points in the observation group. The differences were significant between the two groups ( t=14.02, 8.07, 11.29, all P<0.01). Conclusions:The EAERI support strategy is feasible and effective. The implementation of the EAERI support strategy can reduce the degree of injury when the second victim of the nurse restores the safety incident and improve the degree of support.

Cultivating innovative medical talents is a key strategy for enhancing a hospital's core competitiveness.Taking Zhejiang Cancer Hospital as a case study,this paper constructs a lifelong training system for innovative medical talents based on the"Triple-Phase Cultivation Framework(three stages,four integrations,five mechanisms)".This system delineates the cultivation cycle in-to three stages aligned with talent development trajectories:the"30s Start-up Phase"(young talents under 35),the"40s Growth Phase"(core professionals under 45),and the"50s Breakthrough Phase"(academic leaders under 50).It implements a four-dimensional cultivation model integrating medicine with research,education,engineering/informatics,and industry.Furthermore,a com-prehensive guarantee mechanism is established,encompassing policies & systems,platform re-sources,project drivers,financial investment,and talent teams.Practice demonstrates that this system has significantly enhanced talent development effectiveness.Over the past five years,the hospital has established 2 academician workstations and recruited 10 academician teams.The annual number of postdoctoral researchers has surged from 4 in 2020 to 58 in 2024.A total of 71 innova-tive talents have been selected across three batches,with 69 recognitions in provincial/ministerial-level talent programs,placing the hospital among the leaders within hospitals directly under the Zhejiang Provincial Health Commission.Notably,the hospital achieved a"zero breakthrough"in in-dependently cultivating national-level talents,including recipients of the National Ten-Thousand Talent Program(Young Top Talents)and the Postdoctoral Innovative Talent Support Program.The"Triple-Phase Cultivation Framework"establishes a replicable paradigm for nurturing innovative medical talents through its full-career-cycle approach,multidisciplinary integration,and systematic support mechanisms,offering valuable insights for talent strategies in specialized cancer hospitals.

Objective:To explore the effect of EAERI (E: environment; A: accompany; E: emotion; R: respect; I: information) support strategies in the application of nurse second victims in restoring the passage of a patient safety incident, and to provide support to nurse second victims experiencing a safety incident in restoring the incident and mitigating secondary victimization from the incident.Methods:The method of historical comparison was adopted. A convenience sampling method was used to select nurses who experienced patient safety events in Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences) from January 2023 to February 2024 as the study subjects, which were divided into observation group and control group by the historical control grouping method. The observation group used the EAERI support strategy for patient safety incident reduction, and the control group used the conventional reduction method. The second victims of the nurses in both groups were assessed for their level of harm and support in the patient safety incident using the Second Victim Experience and Support Tool before and after the event reduction, respectively.Results:A total of 124 second victims completed the study. There were 63 cases in the control group, including 13 males and 50 females, with an age of (30.24 ± 4.91) years old. There were 20 males and 41 females in the observation group, with an age of (30.85 ± 5.50) years old. Before the restoration event, there was no significant differences in the total scores of victim experience and support, the degree of injury and the degree of support between the two groups (all P>0.05). The total scores of victim experience and support, the degree of injury and the degree of support were (89.35 ± 10.69), (44.57 ± 6.19), (44.78 ± 9.40) points in the control group, and (64.13 ± 9.36), (33.56 ± 8.84), (30.56 ± 3.17) points in the observation group. The differences were significant between the two groups ( t=14.02, 8.07, 11.29, all P<0.01). Conclusions:The EAERI support strategy is feasible and effective. The implementation of the EAERI support strategy can reduce the degree of injury when the second victim of the nurse restores the safety incident and improve the degree of support.

Cultivating innovative medical talents is a key strategy for enhancing a hospital's core competitiveness.Taking Zhejiang Cancer Hospital as a case study,this paper constructs a lifelong training system for innovative medical talents based on the"Triple-Phase Cultivation Framework(three stages,four integrations,five mechanisms)".This system delineates the cultivation cycle in-to three stages aligned with talent development trajectories:the"30s Start-up Phase"(young talents under 35),the"40s Growth Phase"(core professionals under 45),and the"50s Breakthrough Phase"(academic leaders under 50).It implements a four-dimensional cultivation model integrating medicine with research,education,engineering/informatics,and industry.Furthermore,a com-prehensive guarantee mechanism is established,encompassing policies & systems,platform re-sources,project drivers,financial investment,and talent teams.Practice demonstrates that this system has significantly enhanced talent development effectiveness.Over the past five years,the hospital has established 2 academician workstations and recruited 10 academician teams.The annual number of postdoctoral researchers has surged from 4 in 2020 to 58 in 2024.A total of 71 innova-tive talents have been selected across three batches,with 69 recognitions in provincial/ministerial-level talent programs,placing the hospital among the leaders within hospitals directly under the Zhejiang Provincial Health Commission.Notably,the hospital achieved a"zero breakthrough"in in-dependently cultivating national-level talents,including recipients of the National Ten-Thousand Talent Program(Young Top Talents)and the Postdoctoral Innovative Talent Support Program.The"Triple-Phase Cultivation Framework"establishes a replicable paradigm for nurturing innovative medical talents through its full-career-cycle approach,multidisciplinary integration,and systematic support mechanisms,offering valuable insights for talent strategies in specialized cancer hospitals.

Objective:To investigate whether ultra-high dose rate (FLASH) irradiation can reduce radiation-induced intestinal injuries of mice compared to conventional dose rate (CONV) irradiation.Methods:Both FLASH and CONV irradiation were delivered with electron beam, with dose rates of 750 Gy/s and 0.5G y/s, respectively. A total of 105 mice were randomly divided into groups using a simple randomization method. Twenty-one mice were selected for weight observation, 7 mice in each group. After 9 Gy FLASH and CONV irradiation on the abdomen, the weight changes of mice were measured every other day, and compared among three groups. Twenty-four mice were selected for pathological examination including 5 mice in the control group. Three-and-a-half-day days after 12 Gy FLASH ( n=10) and CONV irradiation ( n=9) on the abdomen, the intestines of the mice were taken. Pathological sections were stained with hematoxylin-eosin (HE) to compare the number and percentage of regenerated crypts of the small intestine between two groups. After 12 Gy FLASH ( n=10) and CONV irradiation ( n=10) on the abdomen, the survival of 20 mice was observed. After FLASH using 4.5 Gy×2 times ( n=10) and CONV irradiation at 9 Gy×1 time ( n=10) on the abdomen, the weight changes were observed. After FLASH using 6 Gy×2 times ( n=10) and CONV irradiation at 12 Gy×1 time ( n=10) on the abdomen, the survival of mice was observed. The time interval between two irradiation was 1 min. EBT3 film was employed to monitor the actual exposure dose of the mice. The variables conforming to normal distribution were expressed by Mean±SD. Inter group comparison was performed by independent t-test. The survival of mice among different groups was compared by log-rank test. Results:After 9 Gy of abdominal irradiation, the mean weight of mice in the FLASH group was significantly higher than that in the CONV group. The weight of mice in the FLASH and CONV groups was (19.8±0.8) g and (18.0±1.8)g ( P=0.036) at 7 days after irradiation, (22.0±1.0)g and (21.2±0.5)g ( P=0.075) at 15 days after irradiation, and (24.2±1.4)g and (22.0±1.2)g ( P=0.012) at 25 days after irradiation, respectively. After 12 Gy irradiation, the mean survival of mice in FLASH and CONV groups was 4 days and 4.7 days ( P=0.029). After 12 Gy total abdominal irradiation, the mean number of intestinal regenerative crypts in the FLASH and CONV groups was 2.9/mm and 1.2/mm ( P=0.041), and the percentage of intestinal regenerative crypts was 34.1% and 14.1%, respectively. The survival of mice irradiated by FLASH using 6 Gy×2 times was longer compared with that of mice after CONV irradiation at 12 Gy×1 time. The weight of mice after 4.5 Gy×2 times irradiation was higher than that of mice after CONV irradiation at 9 Gy×1 time. Conclusion:Weight, survival and the number of intestinal regenerative crypts in the FLASH group are higher than those in the CONV group after irradiation, indicating that radiation-induced intestinal injury caused by FLASH irradiation is slighter than that of CONV irradiation.