1.Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses.
Liping BAI ; Jin YANG ; Siting YU ; Zhongzheng XIANG ; Yuanyuan ZENG ; Meiling SHEN ; Xiaorong KOU ; Qinjie WU ; Changyang GONG
Acta Pharmaceutica Sinica B 2024;14(2):821-835
Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H2O2), which is then used in the Cu+-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.
2.Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy.
Yunzhu LIN ; Xiang WANG ; Shi HE ; Zhongxin DUAN ; Yunchu ZHANG ; Xiaodong SUN ; Yuzhu HU ; Yuanyuan ZHANG ; Zhiyong QIAN ; Xiang GAO ; Zhirong ZHANG
Acta Pharmaceutica Sinica B 2024;14(2):854-868
Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.
3.The mediating effect of work motivation on the relationship between work-family conflict and invisible absence among clinical nurses
Hua HUANG ; Yuanyuan ZHANG ; Hongchun XIANG
Chinese Journal of Practical Nursing 2024;40(9):673-679
Objective:To explore the mediating effect of work motivation of clinical nurses between work-family conflict and invisible absence, so as to provide a basis for reducing nurses′ invisible absence.Methods:From September to December 2022, a cross-sectional survey was conducted to investigate the mediating effect of work motivation between the work-family conflict and invisible absence by using the general information questionnaire, Work-Family Conflict Scale, Work Motivation Scale and Stanford Invisible Absence Scale among 522 nurses by convenience sampling.Results:The valid questionnaires were 511 samples. There were 15 male nurses and 496 female nurses among the 511 nurses. The work-family conflict of clinical nurses had a positive effect on invisible absence ( r=0.319, P<0.05), and work motivation had a partial mediating effect between work-family conflict and invisible absence (the effect value was 0.082), the mediating effect accounted for 35.00% of the total effect. Conclusions:Nursing managers and nurses themselves should take a variety of ways to reduce the work-family conflict, promote the work-family balance of nurses, and improve their work motivation, so as to reduce their invisible absence and promote the healthy development of clinical nurses.
4.The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"
Wanjie YANG ; Xianduo LIU ; Ximo WANG ; Weiguo XU ; Lei ZHANG ; Qiang FU ; Jiming YANG ; Jing QIAN ; Fuyu ZHANG ; Li TIAN ; Wenlong ZHANG ; Yu ZHANG ; Zheng CHEN ; Shifeng SHAO ; Xiang WANG ; Li GENG ; Yi REN ; Ying WANG ; Lixia SHI ; Zhen WAN ; Yi XIE ; Yuanyuan LIU ; Weili YU ; Jing HAN ; Li LIU ; Huan ZHU ; Zijiang YU ; Hongyang LIU ; Shimei WANG
Chinese Critical Care Medicine 2024;36(2):195-201
The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.
5.Practice and reflection on the construction of intelligent medical education system
Chuanwei XUE ; Yuanyuan WANG ; Jie XIANG ; Peipei QIN ; Fang WANG
Modern Hospital 2024;24(6):981-984
Based on the practice of intelligent construction of medical education in Fuwai Hospital of CAMS&PUMC in recent years,this article deeply discusses the important role of R & D management thinking of integrated product development(Integrated Product Development,IPD)in the intelligent construction of hospital education.By building an intelligent platform for medical education,we can help hospitals improve their teaching strength in an all-round way,provide strong technical support for the performance evaluation of third-tier public hospitals,greatly improve the operational efficiency of hospitals,and firmly grasp the pulse of the times.to provide new solutions for the construction of hospital education intelligence system.
6.Effect of AIDS and tuberculosis co-infection on CD8+T lymphocytes
Jingmin NIE ; Xiang DU ; Yuanyuan YU ; Li TIAN ; Jun SANG ; Wei SUN
Chinese Journal of Infection and Chemotherapy 2024;24(4):390-394
Objective To investigate the effects of AIDS and tuberculosis(TB)co-infection on CD8+T lymphocytes.Methods Serum CD8+T cells and CD4+T cells were analyzed and compared between human immunodeficiency virus(HIV)alone patients(n=200),TB alone patients(n=200),and HIV/TB co-infection patients(n=200).Results CD8+T cells were significantly higher in HIV alone group compared to HIV/TB co-infection group and TB alone group(x2=128.779,P<0.001).The level of CD8+T lymphocytes in HIV/TB co-infection group and HIV alone group was higher than normal level(ZHIV/TB=8.343,PHIV/TB<0.001,ZHIV=7.988,PHIV<0.001).The CD8+T cells in TB alone group decreased significantly compared with normal levels(ZTB=8.682,PTB<0.001).The levels of CD4+T cells in the three groups of patients were all lower than normal(ZHIV=11.088,PHIV<0.001,ZTB=5.562,PTB<0.001,ZHIV/TB=12.077,PHIV/TB<0.001).The stratified analysis of CD8+T cell levels by CD4+T cell counts,showed that when CD4+T cell count was≤100 cells/μL,the level of CD8+T cells in HIV alone group was higher than that in TB alone group.HIV alone group had higher CD8+T cells than HIV/TB co-infection group,and the level of CD8+T cells in HIV/TB co-infection group was significantly lower than normal(Z0-100=1.604,P0-100=0.109).When CD4+T cells ≥101 cells/μL,HIV/TB co-infection group had higher CD8+T cells than TB alone group.HIV alone group had higher CD8+T cells than TB alone group.When CD4+T cells>500 cells/μL,CD8+T cell levels were within the normal range in all three groups of patients.Taking the HIV alone group as a reference,with the decrease of CD4+T cell count,the CD8+T cell count decreased more significantly in TB alone group and HIV/TB co-infection group than in HIV alone group(slope was 0.344 and 0.216,respectively,P<0.001).Conclusions With the decline of CD4+T cells,both HIV/TB co-infection and TB alone are associated with decrease in CD8+T cells,and the decrease in the TB alone group is more prominent.
7.Clinical Questions Construction in Clinical Practice Guidelines: Based on Case-guided Approach
Yicheng GAO ; Zijin YU ; Yaqi WANG ; Rui FANG ; Cheng WANG ; Yuanyuan LI ; Yingjie DENG ; Xue BAI ; Wenyuan XIANG ; Yutong FEI
Medical Journal of Peking Union Medical College Hospital 2024;16(1):198-203
Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.
8.Study on biological characterization and immuno-protection of Trueperella pyo-genes from a bovine lung
Yuanyuan WANG ; Lezhen YANG ; Xiang YUAN ; Xu PENG ; Xinyu LIU ; Yuanyi PENG ; Nengzhang LI
Chinese Journal of Veterinary Science 2024;44(6):1156-1164
Trueperella pyogenes(TP),an important livestock and poultry pathogen,can cause vari-ous diseases such as suppurative pneumonia,arthritis,and mastitis in animals.The newly brought calves of one cattle farm occurred respiratory diseases and accompanied death in Yunyang,Chongqing,based on post-mortem examination,suppuration nodules were found in the lungs,and microscopic observation of tissue smears with staining showed that a lot of short rod shape bacteri-a were in tissue.The bacteria were isolated and purified from the clinic lung tissue and analyzed by 16S rRNA sequence,the result showed the infectious bacteria was Rueperella pyogenes,and it was nominated as TpCQ-yy1.TpCQ-yy1 cultured on rabbit blood agar plates could form double-zone hemolysis,and can utilize glucose and lysine.Interestingly,the drug-resistance characteristics of TpCQ-yy1 partially changed along with the variation of the culture medium.Pathogenicity analysis showed that TpCQ-yy1 could make suppurative lesions in the lungs of mice infected via the thorac-ic and intraperitioneal route,and later led mice to death,while the subcutaneous and intramuscular routes of infection had only suppurative foci at the site of injection and were dose-dependent and non-lethal.The genome size of TpCQ-yy1 is 2.335 Mb,which encoding 2 107 proteins,and the phy-logenetic analysis showed TpCQ-yy1 is close to Trueperella pyogenes TP1 strain but away from other strains.TpCQ-yy1 infection could promote the secretion of inflammatory factors of macro-phage.TpCQ-yy1 inactivated bacterial vaccine and recombinant hemolysin(rPLO)subunit vaccine could induce high levels of antibodies production in mice immunized via subcutaneous and muscle route,but only provided 33.3%-66.7%protection to the immunized mice against TpCQ-yyl infec-tion via intraperitioneal route.This research provides a fundamental basis for the understanding of the biological characteristics,pathogenicity,and prevention and control of Trueperella pyogenes.
9.One case report of adjuvant antidepressant therapy with vitamin D and calcium
Hao SHI ; Xiaochun CHENG ; Lingquan KONG ; Liyuan MU ; Xiang ZHANG ; Yuanyuan WANG ; Hongyuan LI ; Guosheng REN ; Kainan WU
Chinese Journal of Endocrine Surgery 2024;18(4):591-592
Depression is a common mental illness in adolescents, and some patients do not respond well after medication, which may be partly related to vitamin D deficiency and insufficient calcium intake. This paper reports a 15-year-old patient with depression, whose condition was still unstable and the effect was not good despite routine use of antidepressant drugs and psychological intervention. After adequate supplementation of vitamin D and calcium, the patient's depression improved significantly, and the follow-up for 4 months, the condition was stable and did not recur.
10.Correlation between physical fitness condition and depressive symptoms in adolescents
Chinese Journal of School Health 2023;44(5):654-658
Objective:
To explore the relationship between adolescents physical fitness and depressive symptoms, and to provide reference for the early prevention and intervention of depressive symptoms and improvement of physical fitness in Chinese adolescents.
Methods:
From September to December 2021, a total of 8 102 adolescents were selected by random cluster sampling method in Shanghai, Urumqi, Changsha and Kunming. The Center for Epidemiologic Studies Depression Scale(CES-D) was used to investigate the depressive symptoms, and completed grip strength, standing long jump, 50 m running, modified sitting forward flexion, 20 s repeated traverse, 30 s sit ups, 20 m round trip running (20 m SRT) test. χ 2 test, Goodman Kruskal Gamma and Logistic regression analysis were used to analyze the relationship between physical fitness index(PFI) and depressive symptoms.
Results:
The overall detection rate of depressive symptoms in adolescents with high level PFI was 23.4%, and the detection rate of low level adolescents was 26.3%, with a statistically significant difference ( χ 2=6.73, P =0.01). There was a significant positive correlation between PFI and depressive symptoms in the high school group ( G=0.09, P <0.05) and the boy group ( G=0.12, P < 0.05 ), and there was no significant association between PFI and depressive symptoms in the junior high school group and the girl group ( P >0.05). After adjusting for gender and age in the Logistic regression model, compared with those with high PFI, the risk of depressive symptoms in those with low PFI was 1.18 times (95% CI =1.05-1.33).
Conclusion
There is a correlation between physical fitness and depressive symptoms in adolescents. Adolescents with low PFI are at higher risk of developing depressive symptoms than those with high PFI.


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