1.Spatiotemporally delivery of Cas9 ribonucleoprotein/DNAzyme logic systems using near-infrared upconversion nanomachine for precise immunotherapy.
Chao CHEN ; Shiyu DU ; Qianglan LU ; Xueting SHEN ; Shuai DING ; Lihua QU ; Yamei GAO ; Zhiqiang YIN ; Zhe LI ; Yujun SONG ; Xin HAN
Acta Pharmaceutica Sinica B 2025;15(10):5431-5443
Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C2P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn2+ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C2P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.
2.Construction of a value evaluation index system for health management and logistics positions in public hospitals
Zhao LONG ; Chunping LI ; Qiwen XIAO ; Lan LI ; Yuan ZHOU ; Shiyu YANG ; CIREN SUOLANG ; Jiangbo DU ; YANGZONG DAWA ; Lingli DING
Modern Hospital 2025;25(2):234-237,242
Objective To develop a value evaluation index system for health management and logistics positions in pub-lic hospitals,providing a research tool for future performance evaluations and salary reform.Methods Literature review,focus group interviews,and the point-factor method were employed to establish an initial index pool.A public hospital in Guangzhou was selected as a case study.Delphi expert consultation was then utilized to refine and finalize the indicators for the evaluation system.Results For the two rounds of Delphi expert consultation,the response rates were 87.5%and 100.0%,with the expert authority coefficient of 0.812.The Kendall's W coordination coefficients were 0.796 and 0.624 for the first round,and 0.747 and 0.918 for the second,(all<0.001).The coefficients of variation ranged from 0.157 to 0.265 for the first round and from 0.108 to 0.230 for the second round.Experts provided four suggestions,leading to the removal of one secondary indicator and modifications to the definitions of three others.Finally,the evaluation system consists of 4 primary indicators and 12 secondary indicators.Conclusion This system can provide a research tool and reference for the follow-up performance evaluation,improve the salary reform of public hospitals,and promote the high-quality development of public hospitals.
3.Construction of a value evaluation index system for health management and logistics positions in public hospitals
Zhao LONG ; Chunping LI ; Qiwen XIAO ; Lan LI ; Yuan ZHOU ; Shiyu YANG ; CIREN SUOLANG ; Jiangbo DU ; YANGZONG DAWA ; Lingli DING
Modern Hospital 2025;25(2):234-237,242
Objective To develop a value evaluation index system for health management and logistics positions in pub-lic hospitals,providing a research tool for future performance evaluations and salary reform.Methods Literature review,focus group interviews,and the point-factor method were employed to establish an initial index pool.A public hospital in Guangzhou was selected as a case study.Delphi expert consultation was then utilized to refine and finalize the indicators for the evaluation system.Results For the two rounds of Delphi expert consultation,the response rates were 87.5%and 100.0%,with the expert authority coefficient of 0.812.The Kendall's W coordination coefficients were 0.796 and 0.624 for the first round,and 0.747 and 0.918 for the second,(all<0.001).The coefficients of variation ranged from 0.157 to 0.265 for the first round and from 0.108 to 0.230 for the second round.Experts provided four suggestions,leading to the removal of one secondary indicator and modifications to the definitions of three others.Finally,the evaluation system consists of 4 primary indicators and 12 secondary indicators.Conclusion This system can provide a research tool and reference for the follow-up performance evaluation,improve the salary reform of public hospitals,and promote the high-quality development of public hospitals.
4.Correlation analysis between complement C3,C4,CRP,ESR and disease activity in systemic lupus erythematosus
Jinghong WANG ; Lu PAN ; Bingru LU ; Shiyu ZHAO ; Shan DING ; Yiqing LIU
International Journal of Laboratory Medicine 2024;45(11):1327-1330,1337
Objective To investigate the correlation between complement C3,C4,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR)and disease activity of systemic lupus erythematosus(SLE).Methods A total of 69 SLE patients admitted to the hospital from January to December 2021 were selected as the SLE group,and 70 healthy individuals were selected as the control group during the same period.The changes of serum related indicators were compared between the SLE group and the control group.According to systemic lupus erythematosus disease activity index(SLEDAI),SLE patients were divided into mild active group(27 cases)and moderate and severe active group(42 cases).The changes of related indicators were compared between the two groups.Spearman correlation analysis was used to analyze the correlation between SLEDAI score and serum related indicators.Receiver operating characteristic(ROC)curve was used to ana-lyze the validity of diagnosis of disease severity.Results Compared with the control group,the levels of serum complement C3 and C4 in the SLE group were decreased,and the levels of CRP and ESR were increased,the differences were statistically significant(P<0.05).Compared with the mild group,the levels of serum com-plement C3 and C4 in the moderate and severe group were decreased,and the levels of CRP and ESR were in-creased,and the differences were statistically significant(P<0.05).The SLEDAI score of SLE patients was positively correlated with serum CRP and ESR levels(P<0.05),and negatively correlated with serum com-plement C3 and C4 levels(P<0.05).The area under the curve(AUC)of CRP,ESR,complement C3 and C4 were 0.716,0.875,0.872 and 0.856,respectively,the sensitivity were 59.52%,85.71%,78.57%and 78.79%,respectively,and the specificity were 79.83%,81.67%,86.79%and 86.54%,respectively.Conclu-sion Serum complement C3,C4,CRP and ESR are correlated with the progression of SLE,and play auxiliary roles in the disease activity stage of SLE.
5.Cross-Sectional Study of Nutritional Service Capacity for Infants and Toddlers in Urban and Rural Medical Facilities in Sichuan Province
Yanxi DING ; Shiyu ZHANG ; Mengtong YANG ; Sijia CHEN ; Ju ZHANG ; Piao ZHANG ; Ming LI ; Danping SU ; Hongli DONG ; Yishan GUO ; Wenya YIN ; Guo ZENG
Journal of Sichuan University (Medical Sciences) 2024;55(4):911-917
Objective To investigate and analyze the current status and challenges of infant and toddler nutritional services in urban and rural medical facilities in Sichuan Province.Methods In 2022,a questionnaire survey was conducted to collect data on infant and toddler nutritional services,including feeding guidance,physical growth assessment,and micronutrient deficiency screening,as well as information on personnel and tools in medical facilities throughout Sichuan Province.The provision of nutritional services was analyzed and the urban-rural disparities were assessed.Results A total of 2206 medical facilities(29.1%from urban areas and 70.9%from rural areas)were investigated.Only 35.8%of medical facilities provided all three types of nutritional services.Specifically,the overall service provision rates were high for feeding guidance(94.6%)and physical growth assessment(85.0%),but lower for micronutrient deficiency screening(37.4%).Rural facilities exhibited significantly lower rates than their urban counterparts for both physical growth assessment and micronutrient deficiency screening(P<0.05).The provision rates of feeding guidance ranged from 70.6%to 93.2%,with responsive feeding guidance being the least implemented(70.6%),particularly in rural areas compared to urban areas(P<0.05).Rates for physical growth assessment and micronutrient deficiency screening ranged from 75.3%to 81.8%and 23.6%to 30.8%,respectively,both showing lower rates in rural settings compared to urban ones(P<0.05).Nutrition service providers were predominantly nurses(52.3%)and clinical practitioners(43.4%).The availability of dietary assessment tools ranged from 7.7%to 15.9%,significantly lower in rural areas compared to urban areas(P<0.001),while physical measurement tools were widely available at rates of 94.6%to 98.5%.Conclusion At present,the infant and toddler nutritional service provisions of medical facilities in Sichuan Province are incomplete,particularly so in the implementation of feeding guidance,physical growth assessment,and micronutrient deficiency screening.There is a notable shortage of personnel and necessary tools,with rural areas facing more significant challenges.Enhancing the overall capacity of infant and toddler nutritional services in Sichuan Province is essential,with specific attention needed for rural healthcare settings.
6.Prospects and advantages of artificial intelligence language models in clinical decision support systems
Shiyu ZHOU ; Min JIANG ; Di DU ; Haiwei DING ; Ying'ao YE
Chinese Journal of Modern Nursing 2024;30(36):5027-5031
With the continuous development of artificial intelligence (AI) language models, their preliminary application in the medical field has demonstrated tremendous potential. AI language models hold significant promise for development and application in nursing clinical decision support systems, showcasing distinct advantages while facing various challenges. This review aims to explore the prospects, advantages, and challenges of integrating AI language models into nursing clinical decision support systems against the backdrop of advancing informatization and intelligent healthcare. It provides insights and references for future applications of AI language models in nursing clinical decision-making.
7.Prospects and advantages of artificial intelligence language models in clinical decision support systems
Shiyu ZHOU ; Min JIANG ; Di DU ; Haiwei DING ; Ying'ao YE
Chinese Journal of Modern Nursing 2024;30(36):5027-5031
With the continuous development of artificial intelligence (AI) language models, their preliminary application in the medical field has demonstrated tremendous potential. AI language models hold significant promise for development and application in nursing clinical decision support systems, showcasing distinct advantages while facing various challenges. This review aims to explore the prospects, advantages, and challenges of integrating AI language models into nursing clinical decision support systems against the backdrop of advancing informatization and intelligent healthcare. It provides insights and references for future applications of AI language models in nursing clinical decision-making.
8.Comparison of clinical effects of a novel stent assisted intestinal bypass and temporary loop ileostomy in laparoscopic low anterior resection of rectal cancer
Liushiyang XU ; Shiyu HU ; Wanbo HUANG ; Jianming XIE ; Jiabin YANG ; Yongfang YIN ; Haixiang DING ; Zhilong YAN
Chinese Journal of General Surgery 2023;38(6):401-406
Objective:To compare the clinical value of stent assisted intestinal bypass and temporary loop ileostomy in laparoscopic low anterior resection of rectal cancer.Method:In this retrospective analysis, 57 patients undergoing laparoscopic low anterior resection for rectal cancer in the First Affiliated Hospital of Ningbo University from Jan 2020 to Jan 2022 were divided into intestinal bypass group (36 cases) and loop ileostomy group (21 cases).Result:There were no significant differences in postoperative GI function recovery and postoperative complication rate between the two groups (all P>0.05). The levels of albumin, prealbumin and hemoglobin in the intestinal bypass group were better than those in the ileostomy group when evaluated on 3rd months after operation [(40.5±2.3) g/L vs. (38.1±2.6)g/L、(26.4±2.7)mg/dl vs. (24.5±2.0)mg/dl、(137.6±5.9) g/L vs. (134.0±7.0) g/L, t=3.605、2.743、2.085, all P<0.05]. Hospital expenses of the intestinal bypass group was lower [(571 000±7 500) yuan vs. (69 300±9 100) yuan, t=-5.477, P<0.05]. Conclusion:Compared with traditional ileostomy, the stent assisted intestinal bypass reduces trauma with lower expenses and improves patients' status after laparoscopic low anterior resection for rectal cancer.
9.Potential Mechanism of Action of Qiangxin Decoction (强心汤) for Chronic Heart Failure Based on Network Pharmacology and Molecular Docking
Meiling MAO ; Jianqi LU ; Liyu XIE ; Yan PANG ; Ding ZHANG ; Weiqi SHI ; Shuihua LIU ; Zongyu CAI ; Shiyu ZHANG ; Min HUANG
Journal of Traditional Chinese Medicine 2023;64(20):2132-2137
ObjectiveTo reveal the targets and molecular mechanisms of the action of Qiangxin Decoction (强心汤) for the treatment of chronic heart failure based on the combination of network pharmacology and molecular docking. MethodsThe active ingredients of Qiangxin Decoction were retrieved from TCMSP database, and the targets of chronic heart failure were screened by searching GeneCards, OMIM, TTD, PharmGkb, and DrugBank databases, and the intersections were taken to obtain the intersecting targets of Qiangxin Decoction for the treatment of chronic heart failure. STRING platform was used to construct the protein-protein interaction network (PPI), Cytoscape 3.8.0 software was used to calculate the network topology to screen the core targets, and R 4.2.3 was used to construct the “active ingredient-target” network by analyzing the GO enrichment analysis and KEGG pathway enrichment analysis. AutoDock 1.5.7 was used for molecular docking to predict the binding performance of active ingredients and core targets. ResultsSeventy-five intersecting targets were identified for the treatment of chronic heart failure with Qiangxin Decoction, among which the core targets were estrogen receptor 1 (ESR1, degree value=7), nuclear receptor coactivator 1 (NCOA1, degree value=8), glucocorticoid receptor (NR3C1, degree value=7), and nuclear receptor coactivator 2 (NCOA2, degree value=7). GO enrichment analysis showed that the top 3 items with the smallest P value in molecular function were G protein-coupled amine receptor activity, postsynaptic neurotransmitter receptor activity, and neurotransmitter receptor activity (P<0.01); the top 3 items with the smallest P value in biological process were adenylyl cyclase-activated adrenergic receptor signaling pathway, adrenergic receptor signaling pathway, and adenylyl cyclase-regulated G protein-coupled receptor signaling pathway (P<0.01); the top 3 items with the smallest P values in cellular composition were components of the postsynaptic membrane, synaptic membrane, and presynaptic membrane (P<0.01). KEGG enrichment analysis showed that the top 5 key signaling pathways were neuroactive ligand-receptor interactions, calcium signaling pathway, dopaminergic synapses, cocaine addiction, and cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathway. The molecular docking results showed that lignans and isoflavones had lower binding energies and more structural stability with the four core targets (ESR1, NCOA1, NR3C1, NCOA2). ConclusionThe treatment of chronic heart failure by Qiangxin Decoction was associated with neuroactive ligand-receptor interactions, calcium signaling pathway, dopaminergic synapses, chemoattractant-receptor activation, cGMP-PKG signaling pathway, lipids and atherosclerosis, and cAMP signaling pathway, and lignans and isoflavones may be the core active compounds in its treatment of chronic heart failure.
10.Neuron stem cell NLRP6 sustains hippocampal neurogenesis to resist stress-induced depression.
Chuanfeng TANG ; Qiaona WANG ; Jingyan SHEN ; Congying WANG ; Hong DING ; Shiyu WEN ; Fan YANG ; Ruiqing JIAO ; Xingxin WU ; Jianmei LI ; Lingdong KONG
Acta Pharmaceutica Sinica B 2023;13(5):2017-2038
Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.

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