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.Burkitt lymphoma of prostate: a case report
Meiling SHEN ; Qingmeng LIU ; Zhaoming WANG ; Xiaoxiang HE
Chinese Journal of Urology 2024;45(6):473-474
A case of secondary Burkitt lymphoma of prostate was reported. A 39-year-old patient was admitted to the hospital with no apparent cause for impaired urination with frequent/urgent urination. CT scan of the whole abdomen showed irregular soft tissue mass of the prostate, involving the bladder and rectum, and mild obstructive hydronephrosis of the renal pelvis and ureter. Biopsy of the prostatic mass was performed, and the pathological findings were consistent with Burkitt lymphoma. PET-CT examination showed multiple lesions and lymph node enlargement throughout the body, secondary prostate lymphoma was diagnosed. After diagnosis, the patient was treated with R-DA-EPOCH chemotherapy and followed up for 9 months. Prostate lymphoma is rare and needs to be combined with clinical manifestations and laboratory tests to determine whether it is primary or secondary, but also to distinguish from prostate diseases such as prostatitis and poorly differentiated prostate cancer.
3.The best evidence for the management of ovarian hyper-stimulation syndrome in patients undergoing assisted reproductive therapy
Yu HE ; Zilian WANG ; Yongmei ZHANG ; Xuechun JIANG ; Xuling SHEN ; Meiling XU ; Qun WEI
Journal of Zhejiang University. Medical sciences 2024;53(5):632-640
Objective:To summarize the best evidence for the management of ovarian hyperstimulation syndrome in patients undergoing assisted reproductive therapy.Methods:Evidence related to the management of ovarian hyperstimulation syndrome in patients undergoing assisted reproductive therapy,including guidelines,clinical decision,best clinical practice,systematic evaluation,expert consensus and evidence summary and related original research were systematically searched in UpToDate,BMJ Best Practice,World Health Organization(WHO)website,Guidelines International Network(GIN),National Institute for Health and Clinical Excellence(NICE)website,National Guidelines website,American Society for Reproductive Medicine(ASRM)website,New York Academy of Sciences(NYAS)website,Joanna Briggs Institute(JBI)database,Cochrane Library,CINAHL,PubMed,Wanfang database,CNKI,and China Biomedical Literature Database from inception to May 31,2024.Two researchers independently evaluated the quality of the literature,and a senior researcher made the final decision for literature inclusion.Results:A total of 15 articles were included in the study.Following quality assessment,one article was excluded.The remaining 14 articles included 5 practice guidelines,3 systematic reviews,2 expert consensuses,1 evidence summary,and 3 from UpToDate.Ultimately,27 pieces of evidence were identified across five key aspects:risk assessment,disease monitoring,early prevention,institutional management and health education.Conclusion:The updated evidence indicates that the monitoring and prevention of ovarian hyperstimulation syndrome should start early,personalized treatment plans should be provided for patients,and the rational allocation of treatment resources needs to be promoted to enhance effective management of ovarian hyper-stimulation syndrome.
4.Construction of an evaluation index system for clinical practice bases of nursing graduate students majoring in midwifery from a practical perspective
Xuqian SHEN ; Yufang GAO ; Lei SONG ; Meiling YUAN ; Rui YANG ; Zitong JI ; Longlong WANG
Chinese Journal of Modern Nursing 2024;30(1):55-62
Objective:To establish a comprehensive and detailed evaluation index system for clinical practice bases of nursing graduate students majoring in midwifery, providing reference for promoting the construction of clinical practice bases for nursing graduate students majoring in midwifery in China.Methods:Based on the theoretical framework of international midwifery practice basic skills, an evaluation index system for clinical practice bases of nursing graduate students majoring in midwifery was established through literature analysis and Delphi method. Analytic hierarchy process was used to calculate the weights of indicators at all levels.Results:This study conducted two rounds of consultation with 20 experts. In the two rounds of consultation, the positivity coefficients of experts were 84.38% and 74.07%, and the authority coefficients of the expert groups were 0.91 and 0.94, respectively. The total Cronbach's α coefficients of the index system were 0.930 and 0.965, respectively, and the Kendall harmony coefficients of the overall indicators were 0.230 and 0.297 ( P<0.01). The final evaluation index system for clinical practice bases of nursing graduate students majoring in midwifery included five primary indicators, 14 secondary indicators, and 76 connotation indicators. Conclusions:Based on the service purpose of maternal and child health and the functional positioning of the base, this study constructs a scientific and reliable evaluation index system for clinical practice bases of nursing graduate students majoring in midwifery.
5.Evidence summary on preventive management of high output and dehydration in ileostomy patients
Yingying XU ; Dandan PEI ; Li CHEN ; Huanhuan ZHU ; Meiling XU ; Yajuan WENG ; Xiaofei SHEN
Journal of Clinical Medicine in Practice 2024;28(23):126-131
Objective To retrieve, evaluate, and summarize evidence on preventive management of high output and dehydration in ileostomy patients from both domestic and international sources. Methods Based on the "6S" evidence model, a top-down approach was employed to retrieve evidence on prevention and management of high output and dehydration in ileostomy patients. Databases searched included BMJ best practice, UpToDate, National Guideline Clearinghouse (NGC), National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), Registered Nurses' Association of Ontario (RNAO), Wound Ostomy and Continence Nurses Society (WOCNS), World Council of Enterostomal Therapists (WCET), Medlive Clinical Guidelines website, Joanna Briggs Institute (JBI), Cochrane Library, Embase, PubMed, Web of Science, CNKI, Wanfang Data, China Biology Medicine (CBM), and VIP Database. The search period was from January 2019 to April 2024. Results A total of 13 articles were included after retrieval and screening, comprising 2 guidelines, 2 expert consensuses, 4 systematic reviews, 4 evidence summaries, and 1 clinical decision aid. After translation, summarization, and organization of the included articles, 19 pieces of evidence across 11 categories were formulated, focusing on four items: definition and risk factors of high output in ileostomy, prevention and management strategies related to high output in ileostomy, prevention and management strategies related to dehydration in high-output ileostomy, and follow-up strategies for prevention of high output and dehydration after ileostomy surgery. Conclusion The evidence summarized based on the "6S" evidence model for prevention and management of high output and dehydration in ileostomy patients can provide a reference for clinical practice among healthcare professionals and medical decision-makers, thereby enhancing nursing quality and reducing patient rehospitalization rates.
6.Eligibility of C-BIOPRED severe asthma cohort for type-2 biologic therapies.
Zhenan DENG ; Meiling JIN ; Changxing OU ; Wei JIANG ; Jianping ZHAO ; Xiaoxia LIU ; Shenghua SUN ; Huaping TANG ; Bei HE ; Shaoxi CAI ; Ping CHEN ; Penghui WU ; Yujing LIU ; Jian KANG ; Yunhui ZHANG ; Mao HUANG ; Jinfu XU ; Kewu HUANG ; Qiang LI ; Xiangyan ZHANG ; Xiuhua FU ; Changzheng WANG ; Huahao SHEN ; Lei ZHU ; Guochao SHI ; Zhongmin QIU ; Zhongguang WEN ; Xiaoyang WEI ; Wei GU ; Chunhua WEI ; Guangfa WANG ; Ping CHEN ; Lixin XIE ; Jiangtao LIN ; Yuling TANG ; Zhihai HAN ; Kian Fan CHUNG ; Qingling ZHANG ; Nanshan ZHONG
Chinese Medical Journal 2023;136(2):230-232
7.A tactical nanomissile mobilizing antitumor immunity enables neoadjuvant chemo-immunotherapy to minimize postsurgical tumor metastasis and recurrence.
Tao HE ; Mingxing HU ; Shunyao ZHU ; Meiling SHEN ; Xiaorong KOU ; Xiuqi LIANG ; Lu LI ; Xinchao LI ; Miaomiao ZHANG ; Qinjie WU ; Changyang GONG
Acta Pharmaceutica Sinica B 2023;13(2):804-818
Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8+ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.
8.An engineered xCas12i with high activity, high specificity, and broad PAM range.
Hainan ZHANG ; Xiangfeng KONG ; Mingxing XUE ; Jing HU ; Zikang WANG ; Yinghui WEI ; Haoqiang WANG ; Jingxing ZHOU ; Weihong ZHANG ; Mengqiu XU ; Xiaowen SHEN ; Fengcai YIN ; Zhiyuan AI ; Guangyan HUANG ; Junhui XIA ; Xueqiong SONG ; Hengbin LI ; Yuan YUAN ; Jinhui LI ; Na ZHONG ; Meiling ZHANG ; Yingsi ZHOU ; Hui YANG
Protein & Cell 2023;14(7):538-543
9.Sequential immunization with inactivated SARS-CoV-2 vaccines induces humoral immune responses against Wuhan-Hu1 and Omicron variants
Xiuli SHEN ; Yanling HAO ; Shuhui WANG ; Ying LIU ; Li REN ; Dan LI ; Meiling ZHU ; Jing LI ; Wenqi TANG ; Bin LI ; Yiming SHAO
Chinese Journal of Experimental and Clinical Virology 2023;37(2):121-127
Objective:To explore the ability of sequential immunization regimen inducing neutralizing antibodies against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Wuhan-Hu1 and Omicron variants in mice.Methods:Groups of 6-8-week-old BALB/c mice were primed with two doses of Wuhan-Hu-1 inactivated vaccine, and then boosted with Omicron or Wuhan-Hu-1 inactivated vaccine, respectively. Binding antibodies were tested by enzyme linked immunosorbent assay; and neutralizing antibodies against Wuhan-Hu1 and Omicron variants were analyzed by vesicular stomatitis virus pseudovirus assay system; SARS-CoV-2 specific cellular immune responses were quantified by enzyme-linked immunosorbent spot assay.Results:IgG antibodies against Wuhan-Hu1, Delta and Omicron RBD were enhanced after the second dose of Wuhan-Hu1 inactivated vaccine. Compared with Wuhan-Hu1 inactivated vaccine, the group boosted with Omicron inactivated vaccine improved Wu-RBD and Omic-RBD specific IgG antibodies 1.41 and 1.26 times, and serum neutralizing antibodies against BA.1, BA.2, BA.4/5 and BF.7 were elevated 4.5, 3.4, 12.1 and 6.5 folds, respectively, by sequential immunization. After booster immunization with inactivated Wuhan-Hu1 or Omicron vaccines, Wu-RBD IgA titer was significantly higher than that of one dose inactivated Wuhan-Hu1 vaccine ( P=0.005 7, P=0.006 1). Conclusions:Neutralizing antibodies against Omicron variants were enhanced by sequential immunization with Omicron inactivated vaccine. Specific IgA was significantly enhanced after the third dose of inactivated vaccine.
10.The use of portal vein embolization combined with lenvatinib and a PD-1 inhibitor to treat patients with initially unresectable hepatocellular carcinoma
Bin XU ; Xiaolong LI ; Xiaodong ZHU ; Cheng HUANG ; Yinghao SHEN ; Xudong QU ; Meiling LI ; Jinjin ZHU ; Zhaoyou TANG ; Jian ZHOU ; Jia FAN ; Huichuan SUN
Chinese Journal of Hepatobiliary Surgery 2022;28(1):21-27
Objective:To study the safety and treatment outcomes of portal vein embolization (PVE) combined with lenvatinib plus an anti-programmed death-1(PD-1) antibody to treat patients with initially unreasectable hepatocellular carcinoma (uHCC).Methods:This study retrospectively analyzed the data of six patients with uHCC who received first-line combined systemic therapy with lenvatinib plus an anti-PD-1 antibody, and then underwent pre-hepatectomy PVE at the Department of Liver Surgery at Zhongshan Hospital, Fudan University from May 2019 to November 2020. All enrolled patients were males, aged (54.6±6.2) (ranged 46 to 63) years. Tumor response and liver volume were evaluated by medical imagings once every 2 months (±2 weeks) and evaluated using the Response Evaluation Criteria in Solid Tumours (version 1.1). Patients were followed-up by outpatient interviews or by phone calls to record their survival and tumor outcome status.Results:Three of the six enrolled patients had Barcelona Clinic Liver Cancer stage A and three had stage B disease. One patient achieved a partial response and five patients had stable diseases. The mean ± s. d. future liver remnant (FLR) percentage was (29.0±8.9) % before PVE and the combination therapy, and was (41.3±10.8) % before the last evaluation for liver surgery ( t=10.79, P<0.001). Hepatectomy was carried out in five patients, and one patient who failed to develop significant FLR hypertrophy did not undergo hepatectomy. Grade B post-hepatectomy liver failure and major postoperative complications (i.e. pleural effusion requiring additional percutaneous drainage) occurred in one patient. After a median post-operative follow-up of 4.5 (range: 1.0-12.3) months, all five patients were alive and were tumor free. Conclusion:PVE followed by hepatectomy is feasible in a uHCC patients receiving systemic therapy with lenvatinib and an anti-PD-1 antibody.


Result Analysis
Print
Save
E-mail