1.Advances in DNA origami intelligent drug delivery systems
Zeng-lin YIN ; Xi-wei WANG ; Jin-jing CHE ; Nan LIU ; Hui ZHANG ; Zeng-ming WANG ; Jian-chun LI ; Ai-ping ZHENG
Acta Pharmaceutica Sinica 2024;59(10):2741-2750
DNA origami is a powerful technique for generating nanostructures with dynamic properties and intelligent controllability. The precise geometric shapes, high programmability, and excellent biocompatibility make DNA origami nanostructures an emerging drug delivery vehicle. The shape, size of the carrier material, as well as the loading and release of drugs are important factors affecting the bioavailability of drugs. This paper focuses on the controllable design of DNA origami nanostructures, efficient drug loading, and intelligent drug release. It summarizes the cutting-edge applications of DNA origami technology in biomedicine, and discusses areas where researchers can contribute to further advancing the clinical application of DNA origami carriers.
2.Establishment of an indirect ELISA for detection of antibodies against Cysticercus pisiformis infection based on TPO18 protein
Zexiang WANG ; Yonglu LUO ; Ping XUE ; Liang CHE ; Yousen WANG ; Huitian GOU ; Xia-Olin SUN
Chinese Journal of Veterinary Science 2024;44(6):1213-1222
Cysticercosis,caused by the larval stage of the tapeworm Taenia pisiformis,known as Cysticercus pisiformis,is a parasitic ailment affecting lagomorphs,particularly domestic rabbits,posing a threat to the rabbit industry and the safety of rabbit meat products.This study aims to i-dentify the distribution of the TPO18 antigen in Cysticercus pisiformis and Taenia pisiformis and establish an indirect enzyme-linked immunosorbent assay(ELISA)for detecting antibodies against rabbit cysticercosis.The research involved the prokaryotic expression of the 18 kDa antigen of rabbit Cysticercus pisiformis and the isolation of soluble TPO18 protein post-purification.Immuni-zing rabbits with the TPO18 protein resulted in the production of polyclonal antibodies with a titer of up to 1∶51 200.Western blot analysis validated the antigenicity of the polyclonal antibodies a-gainst total proteins from rabbit Cysticercus pisiformis,Taenia pisiformis and the recombinant TPO18 protein.Immunohistochemistry revealed the distribution of the TPO18 antigen in rabbit Cysticercus pisiformis and Taenia pisiform is,indicating the effective reactivity of the polyclonal antibodies with total proteins from both parasites and the recombinant TPO18 protein.TPO18 an-tigen in rabbit Cysticercus pisiformis predominantly localized in the germinal layer and the paren-chyma,while in Taenia pisiformis,it was mainly present in the suckers,sucker peripheries,collec-ting duct upper cells,and parenchyma.An indirect ELISA based on the TPO18 antigen was devel-oped using the recombinant antigen,and its technical parameters were optimized.The optimized ELISA conditions included a serum dilution of 1∶100,antigen coating concentration of 5 mg/L,coating for 1 h at 37 ℃ followed by overnight incubation at 4 ℃,blocking with 1%BSA for 60 min at 37 ℃,serum reaction for 60 min,secondary antibody dilution at 1∶1 000,secondary antibody incubation for 60 min,substrate reacting for 15 min,with a cutoff value of 0.295.Sensitivity,speci-ficity,and repeatability tests of the ELISA demonstrated high sensitivity and specificity without cross-reactivity with positive sera of rabbit hemorrhagic disease virus,Hepatic coccidiosis,Eimer-ia stiedae,or Toxoplasma gondii.The intra-and inter-assay coefficients of variation were both less than 7%,indicating excellent repeatability.Application of this ELISA,compared to postmortem ex-amination,on 86 clinical serum samples showed a concordance rate of 97.7%.In conclusion,this study successfully established an indirect ELISA for detecting antibodies against rabbit Cysticercus pisiformis,presenting a novel monitoring approach for assessing rabbit infections with Cysticer-cus pisiformis.
3.Mechanism of effect of rosiglitazone on pancreatic cancer in diabetic mice based on impact of PPARy on glucose transport and metabolism
Rui-Ping HU ; Li-Feng SHANG ; He-Jing WANG ; Hong-Xia CHE ; Ming-Liang WANG ; Huan YANG ; Yuan-Yuan JIN ; Fei-Fei ZHANG ; Jian-Ling ZHANG
Chinese Pharmacological Bulletin 2024;40(7):1325-1334
Aim To explore the mechanism of the effect of rosiglitazone(Rsg)on the pancreatic cancer in diabetic mice based on the impact of PPARγ on glu-cose transport and metabolism.Methods A high-fat and high sugar diet combined with STZ was used to construct T2DM model;T2DM mice and normal mice were subcutaneously injected with PANC02 cells to construct a transplanted tumor model.T2DM trans-planted tumor mice and normal transplanted tumor mice were divided into the following groups:Rsg,PPARy inhibitor(PIN-2),rosiglitazone+PPARγ in-hibitor(Rsg+PIN-2),and normal transplanted tumor mice(NDM)and T2DM transplanted tumor mice(DM)were used as control groups,respectively.Tis-sue samples were collected after intervention.Tissue pathological changes were observed by HE staining.The expressions of Ki67 and PCNA proteins were de-tected by immunohistochemistry.Cell apoptosis was detected by TUNEL assay.The expression of PPARγwas detected by immunofluorescence.The expressions of Glucokinase,GLUT2,Nkx6.1,PDX-1RT-PCR were determined by Western blot.Results Rsg could significantly reduce the tumor mass,pathological chan-ges,Ki67 and PCNA expression of transplanted tumors(P<0.05),increase cell apoptosis and the expression of PPARγ,Glucokinase,GLUT2,Nkx6.1,PDX-1 proteins in NDM and DM mice(P<0.05).PIN-2 could reverse the indicator changes caused by Rsg in NDM and DM mice.However,compared with NDM mice,the above related indicators of the DM group mice were more sensitive to Rsg and PIN-2.Conclu-sions Compared to non-diabetic pancreatic cancer,rosiglitazone can more sensitively inhibit the prolifera-tion of pancreatic cancer with T2DM,induce apopto-sis,and reprogram the metabolism of pancreatic cancer with T2DM by activating PPA Rγ and altering the ex-pression of glucose and lipid metabolism genes,there-by exerting an anti-cancer effect.
4.Advances of ENPP1 in tumor and its inhibitors applied in tumor therapy
Xiao-Yu CHE ; Xiao-Ying QIN ; Yan CHEN ; Yu-Ping LIU
Chinese Pharmacological Bulletin 2024;40(10):1830-1836
Ecto-nucleotide pyrophosphatases/phosphodiesterases(ENPPs)are involved in the hydrolysis of different purine nu-cleotides in a range of physiological processes.In recent years,it has also been found to be involved in tumor progression,with ENPP1 often overexpressed in local recurrence and tumor metas-tasis,which is associated with poor prognosis and survival in a range of solid tumors.The role of ENPP1 in tumors is mainly fo-cused on tumor proliferation,metastasis,immunity,recurrence,etc.,and it is speculated that ENPP1 can be used as a prognos-tic indicator for a variety of tumors.ENPP1 promotes the immu-nosuppressive tumor microenvironment by being obliquely in-volved in the regulation of ATP/adenosine homeostasis by com-bining with other components,which crosses with interferon gene stimulators to impair its potent immune response through the hy-drolysis of the effector 2',3'-cyclic GMP-AMP.Therefore,EN-PP1 blockade has become an effective means to induce immune remodeling and inhibit tumorigenesis and development.The ex-isting ENPP1 inhibitors mainly include natural small molecule compounds,nucleotide ENPP1 inhibitors,non-nucleotide EN-PP1 inhibitors,and novel small molecule ENPP1 inhibitors.So far,a small number of ENPP1 inhibitors have been developed and are rarely suitable for in vivo experiments,and they are still in the stage of developing effective compounds or lead com-pounds,and the research on ENPP1 inhibitors needs to be fur-ther studied.This review summarizes and discusses the role of ENPP1 in tumors,and summarizes the current research progress of various ENPP1 agents and their current research progress,in order to provide a reference for further research on the prepara-tion of drug candidates.
5.Study on steaming time and characteristic quality standard of salt-steaming Morinda officinalis based on Q-marker and anti-oxidative activities
Mengyun LIU ; Xiaoying CHE ; Qiuyi LIU ; Yiran QIN ; Ping DING
China Pharmacy 2023;34(9):1048-1052
OBJECTIVE To comprehensively screen the optimal steaming time of salt-steaming Morinda officinalis (SSMO) based on Q-markers and anti-oxidative activities, and to establish characteristic quality standard of the decoction pieces. METHODS The contents of six Q-markers (1-kestose, nystose, 1F-fructofuranosylnystose, inulotriose, inulotetraose and inulopentaose) in SSMO at different steaming time were determined by HPLC-ELSD method simultaneously. The activity of sample extracts to scavenge 4 kinds of oxidative free radical and their iron reduction abilities were determined by visible UV spectrophotometer. The optimal steaming time of SSMO was screened by gray relevance degree and entropy weight technique for order preference by similarity to an ideal solution (TOPSIS)-fusion model method. The contents of six Q-markers in 10 batches of SSMO prepared at the optimal steaming time were determined. HPLC-ELSD fingerprints of SSMO decoction pieces were established. RESULTS The results showed that the contents of six Q-markers were the highest when SSMO was steamed for 3-5 h; and the ability of scavenging DPPH·, ABTS·, PTIO·, ·OH and iron reduction ability was the best at 5 h. There were 20 common peaks in the fingerprints for 10 batches of samples, and the similarities were higher than 0.990. A total of 9 chromatographic peaks were identified, which were D-fructose (peak 1), D(+)-glucose (peak 2), sucrose (peak 3), 1-kestose (peak 4), nystose (peak 5), 1F-fructofuranosylnystose (peak 6), inulotriose (peak X2), inulotetraose (peak X3) and inulopentaose (peak X4). Average contents of six Q-markers were 4.17%, 5.54%, 6.60%, 2.89%, 2.62% and 2.13%, respectively. CONCLUSIONS The optimal steaming time of SSMO is 5 h; the contents of six Q-markers are primarily determined on the basis of dry product, which are no less than 3.03%, 4.11%, 4.87%, 2.15%, 1.96% and 1.58%, respectively. The ratio of Inulin-/Inulo oligosaccharides content is no more than 2.5.
6.Multimorbidity Pattern and Risk for Mortality Among Patients With Dementia: A Nationwide Cohort Study Using Latent Class Analysis
Che-Sheng CHU ; Shu-Li CHENG ; Ya-Mei BAI ; Tung-Ping SU ; Shih-Jen TSAI ; Tzeng-Ji CHEN ; Fu-Chi YANG ; Mu-Hong CHEN ; Chih-Sung LIANG
Psychiatry Investigation 2023;20(9):861-869
Objective:
Individuals with dementia are at a substantially elevated risk for mortality; however, few studies have examined multimorbidity patterns and determined the inter-relationship between these comorbidities in predicting mortality risk.
Methods:
This is a prospective cohort study. Data from 6,556 patients who were diagnosed with dementia between 1997 and 2012 using the Taiwan National Health Insurance Research Database were analyzed. Latent class analysis was performed using 16 common chronic conditions to identify mortality risk among potentially different latent classes. Logistic regression was performed to determine the adjusted association of the determined latent classes with the 5-year mortality rate.
Results:
With adjustment for age, a three-class model was identified, with 42.7% of participants classified as “low comorbidity class (cluster 1)”, 44.2% as “cardiometabolic multimorbidity class (cluster 2)”, and 13.1% as “FRINGED class (cluster 3, characterized by FRacture, Infection, NasoGastric feeding, and bleEDing over upper gastrointestinal tract).” The incidence of 5-year mortality was 17.6% in cluster 1, 26.7% in cluster 2, and 59.6% in cluster 3. Compared with cluster 1, the odds ratio for mortality was 9.828 (95% confidence interval [CI]=6.708–14.401; p<0.001) in cluster 2 and 1.582 (95% CI=1.281–1.953; p<0.001) in cluster 3.
Conclusion
Among patients with dementia, the risk for 5-year mortality was highest in the subpopulation characterized by fracture, urinary and pulmonary infection, upper gastrointestinal bleeding, and nasogastric intubation, rather than cancer or cardiometabolic comorbidities. These findings may improve decision-making and advance care planning for patients with dementia.
7.Guideline for the diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients (version 2023)
Yuan XIONG ; Bobin MI ; Chenchen YAN ; Hui LI ; Wu ZHOU ; Yun SUN ; Tian XIA ; Faqi CAO ; Zhiyong HOU ; Tengbo YU ; Aixi YU ; Meng ZHAO ; Zhao XIE ; Jinmin ZHAO ; Xinbao WU ; Xieyuan JIANG ; Bin YU ; Dianying ZHANG ; Dankai WU ; Guangyao LIU ; Guodong LIU ; Qikai HUA ; Mengfei LIU ; Yiqiang HU ; Peng CHENG ; Hang XUE ; Li LU ; Xiangyu CHU ; Liangcong HU ; Lang CHEN ; Kangkang ZHA ; Chuanlu LIN ; Chengyan YU ; Ranyang TAO ; Ze LIN ; Xudong XIE ; Yanjiu HAN ; Xiaodong GUO ; Zhewei YE ; Qisheng ZHOU ; Yong LIU ; Junwen WANG ; Ping XIA ; Biao CHE ; Bing HU ; Chengjian HE ; Guanglin WANG ; Dongliang WANG ; Fengfei LIN ; Jiangdong NI ; Aiguo WANG ; Dehao FU ; Shiwu DONG ; Lin CHEN ; Xinzhong XU ; Jiacan SU ; Peifu TANG ; Baoguo JIANG ; Yingze ZHANG ; Xiaobing FU ; Guohui LIU
Chinese Journal of Trauma 2023;39(6):481-493
Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.
8.Effectiveness of 13-valent pneumococcal conjugate vaccine against invasive disease caused by serotype 19A in children: a meta-analysis.
Zhao Jun LU ; Yan LIU ; Jian DU ; Jun WANG ; Xin Ren CHE ; Wei JIANG ; Xiao Ping ZHANG ; Wen Wen GU ; Yu Yang XU ; Xue Chao ZHANG ; Jing WANG ; Qi Xin XIE ; Ying Ying YANG ; Lin Tao GU
Chinese Journal of Preventive Medicine 2023;57(12):2181-2187
Objective: Using Meta-analysis to evaluate the vaccine effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against invasive Streptococcus pneumoniae disease (IPD) caused by serotype 19A in children <5 years old. Methods: "Streptococcus pneumoniae infection""invasive pneumococcal disease""13-valent pneumococcal polysaccharide conjugate vaccine""PCV13""effectiveness""infant""child" and related terms were searched from China National Knowledge Infrastructure (CNKI), WANFANG DATA, PubMed, SCOPUS and Web of science with no limited on language, region and research institution. The retrieval time was limited from January 2010 to February 2023 and cohort study, case-control study and randomized controlled trial were included. Data were extracted from eligible studies by two independent reviewers, and after study quality assessment by NOS scale, Meta-analysis was completed using Stata 16.0 software. Results: A total of 2 340 related literatures were searched, and 10 literatures were finally included, including 5 case-control studies and 5 indirect cohort studies, which showed good literature quality. The vaccine effectiveness against serotype 19A IPD of PCV13 in children was 83.91% (95%CI: 78.92%-88.89%), and the subgroup analysis (P=0.240) showed there was no significant difference among the case-control study (VE=87.34%, 95%CI:79.74%-94.94%) and the indirect cohort study (VE=81.30%, 95%CI:74.69%-87.92%). The funnel plot and Egger test suggested that the possibility of publication bias was small. Conclusion: The present evidence indicates that PCV13 has a good vaccine effectiveness against serotype 19A IPD in children, and it is recommended to further increase the vaccination rate of PCV13 to reduce the disease burden of IPD in children <5 years old.
Child
;
Humans
;
Child, Preschool
;
Case-Control Studies
;
Cohort Studies
;
Serogroup
;
Vaccines, Conjugate/therapeutic use*
;
China
;
Pneumococcal Infections/prevention & control*
9.Effectiveness of 13-valent pneumococcal conjugate vaccine against invasive disease caused by serotype 19A in children: a meta-analysis.
Zhao Jun LU ; Yan LIU ; Jian DU ; Jun WANG ; Xin Ren CHE ; Wei JIANG ; Xiao Ping ZHANG ; Wen Wen GU ; Yu Yang XU ; Xue Chao ZHANG ; Jing WANG ; Qi Xin XIE ; Ying Ying YANG ; Lin Tao GU
Chinese Journal of Preventive Medicine 2023;57(12):2181-2187
Objective: Using Meta-analysis to evaluate the vaccine effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against invasive Streptococcus pneumoniae disease (IPD) caused by serotype 19A in children <5 years old. Methods: "Streptococcus pneumoniae infection""invasive pneumococcal disease""13-valent pneumococcal polysaccharide conjugate vaccine""PCV13""effectiveness""infant""child" and related terms were searched from China National Knowledge Infrastructure (CNKI), WANFANG DATA, PubMed, SCOPUS and Web of science with no limited on language, region and research institution. The retrieval time was limited from January 2010 to February 2023 and cohort study, case-control study and randomized controlled trial were included. Data were extracted from eligible studies by two independent reviewers, and after study quality assessment by NOS scale, Meta-analysis was completed using Stata 16.0 software. Results: A total of 2 340 related literatures were searched, and 10 literatures were finally included, including 5 case-control studies and 5 indirect cohort studies, which showed good literature quality. The vaccine effectiveness against serotype 19A IPD of PCV13 in children was 83.91% (95%CI: 78.92%-88.89%), and the subgroup analysis (P=0.240) showed there was no significant difference among the case-control study (VE=87.34%, 95%CI:79.74%-94.94%) and the indirect cohort study (VE=81.30%, 95%CI:74.69%-87.92%). The funnel plot and Egger test suggested that the possibility of publication bias was small. Conclusion: The present evidence indicates that PCV13 has a good vaccine effectiveness against serotype 19A IPD in children, and it is recommended to further increase the vaccination rate of PCV13 to reduce the disease burden of IPD in children <5 years old.
Child
;
Humans
;
Child, Preschool
;
Case-Control Studies
;
Cohort Studies
;
Serogroup
;
Vaccines, Conjugate/therapeutic use*
;
China
;
Pneumococcal Infections/prevention & control*
10.Mediating role of social support and exercise self-efficacy between intrinsic capacity and healthy aging in community-dwelling elderly people
Ping YAN ; Xin JIANG ; Yajie CHE ; Fenghui CHEN ; Xuanxuan YANG ; Xuan MA ; Shan YU
Chinese Journal of Modern Nursing 2023;29(35):4775-4781
Objective:To explore the mediating effect of social support and exercise self-efficacy on the intrinsic capacity of community-dwelling older adults and healthy aging, so to provide a basis for improving the healthy aging of community-dwelling older adults.Methods:From January to July 2022, cluster random sampling was used to select 1 303 community-dwelling older adults from Urumqi City as the research subject. The survey was conducted using the General Information Questionnaire, Healthy Aging Instrument, Intrinsic Capacity Questionnaire, Social Support Rating Scale, and Exercise Self Efficacy Scale for Aged People in Community. The conceptual model was used to explore the relationship among social support, exercise self-efficacy, intrinsic capacity, and healthy aging in community-dwelling older adults. A total of 1 303 questionnaires were distributed, and 1 042 valid questionnaires were collected, with an effective response rate of 80%.Results:Among 1 042 community-dwelling older adults, the scores of the Intrinsic Capacity Questionnaire, Healthy Aging Instrument, Social Support Rating Scale, and Exercise Self Efficacy Scale for Aged People in Community were [1.00 (0, 2.00) ] , [146.00 (133.75, 155.00) ] , [41.00 (36.00, 46.00) ] and [51.00 (39.00, 61.00) ] , respectively. The intrinsic capacity of community-dwelling older adults was negatively correlated with social support, exercise self-efficacy, and healthy aging ( r=-0.112, -0.121, -0.120, P<0.01) , and social support and exercise self-efficacy were positively correlated with healthy aging (r=0.129, 0.113, P<0.01) . Bootstrap mediating effect test showed that the mediating effect of social support and exercise self-efficacy between the intrinsic capacity of community-dwelling older adults and healthy aging was established, with a mediating effect value of -0.477, accounting for 24.75% of the total effect. The path effect value of intrinsic capacity→ social support→ healthy aging was -0.262, accounting for 54.93% of the mediating effect value. The path effect value of intrinsic capacity → exercise self-efficacy→ healthy aging was -0.214, accounting for 44.86% of the mediating effect value. Conclusions:In the community elderly population, social support and exercise self-efficacy can play a mediating role between intrinsic capacity and healthy aging. Community health care providers should pay attention to the internal capacity of the older adults, improve social support and exercise self-efficacy, and thus promote the realization of healthy aging of the older adults.

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