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.Application of rehabilitation nursing based on gratitude extension-construction theory in postoperative patients with endometrial cancer
Yanli ZHOU ; Xing GAO ; Lijuan DANG ; Ning WANG ; Xueting SUN
Chinese Journal of Modern Nursing 2023;29(23):3184-3188
Objective:To explore the application effect of rehabilitation nursing based on gratitude extension-construction theory in postoperative patients with endometrial cancer.Methods:Using the convenient sampling method, a total of 80 patients with endometrial cancer who were admitted to the Affiliated Hospital of Jining Medical University from January 2019 to December 2021 were selected as the research objects. The patients were divided into the observation group (42 cases) and the control group (38 cases) using the random number table method. The control group received routine nursing interventions, while the observation group received rehabilitation nursing interventions based on gratitude extension-construction theory. Psychological distress, gratitude, fear of cancer recurrence, quality of life and pelvic floor function were compared between the two groups before and after intervention.Results:After intervention, the scores of psychological distress, cancer recurrence and Pelvic Floor Distress Inventory score in the observation group were lower than those in the control group, and the scores of gratitude and quality of life in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Rehabilitation nursing based on gratitude extension-construction theory can increase the gratitude level of patients undergoing endometrial cancer surgery, promote the recovery of pelvic floor function, reduce psychological pain and cancer recurrence concerns and improve their quality of life.
3.Analysis of influential factors of cardiotoxicity induced by trastuzumab combined with chemotherapy
Xiaoli ZHU ; Chen LYU ; Xueting DU ; Jiaxun JIAO ; Lingna GAO ; Xia SUN ; Hongfang MA
China Pharmacy 2022;33(8):992-995
OBJECTIVE To analyze the influential factors of cardioto xicity in patients with positive breast cancer of human epidermal growth factor receptor 2(HER-2)treated by trastuzumab combined with chemotherapy. METHODS From April 2017 to January 2021,200 HER-2 positive breast cancer patients receiving pirarubicin + cyclophosphamide combined with sequential paclitaxel+trastuzumab were collected from our hospital. According to the presence or absence of cardiotoxicity ,the patients were divided into cardiotoxicity group and non-cardiotoxicity group. The clinical data and echocardiographic results of the patients were collected,and the influential factors of cardiotoxicity were analyzed. RESULTS Among 200 patients,43 patients suffered from cardiotoxicity with the incidence of 21.5%. The proportion of patients with cardiotoxicity during pirarubicin+cyclophosphamide therapy accounted for 5.5%(11/200),and the proportion of patients with cardiotoxicity during sequential paclitaxel+trastuzumab therapy accounted for 20.5%(41/200);the latter was significantly higher than the former (P<0.01). At the same time ,the decrease of left ventricular ejection fraction during sequential therapy of paclitaxel and trastuzumab was significantly higher than that during pirarubicin+cyclophosphamide therapy [ 14%(12%,17%)vs. 7%(3%,10%),P<0.001]. Compared with patients without cardiotoxicity ,the proportion of patients with cardiotoxicity with a history of hyperlipidemia was significantly higher (P< 0.01),while the proportion of patients receiving dexrazoxane was significantly lower (P<0.01). Results of binary Logistic regression analysis showed that the history of hyperlipidemia [OR =3.672,95% CI(1.499,8.992),P=0.004] and the use of dextrazoxane [OR =0.154,95% CI(0.072,0.330), P<0.001] were associated with the occurrence of cardiotoxicity. CONCLUSIONS Hyperlipidemia is an independent risk factor for cardiotoxicity induced by pirarubicin + cyclophosphamide combined with sequential paclitaxel+trastuzumab in HER 2 positive breast cancer patients ,while the use of dextrazoxane is a protective factor.
4.Effects of basic diseases on clinical characteristics and prognosis of septic shock in children
Hengmiao GAO ; Chaonan FAN ; Xueting CHEN ; Guoyun SU ; Suyun QIAN
Chinese Pediatric Emergency Medicine 2021;28(2):107-110
Objective:To investigate the clinical features and prognosis of septic shock(SS) children with different basic diseases in pediatric intensive care unit (PICU).Methods:The medical records of SS children admitted to PICU at Beijing Children′s Hospital from January 1, 2017 to December 31, 2019 were collected retrospectively.They were grouped according to the presence or absence of basic diseases and types of basic diseases.The clinical characteristics, prognosis and pathogens of SS under different basic diseases were summarized.Results:A total of 218 children with SS were included during the study period, and the overall case fatality rate was 21.6%(47/218). There were 141 cases with basic diseases, accounting for 64.7%(141/218) and 24.1%(34/141) case fatality rate.The mortality rate was highest(37.5%, 17/45) in the malignant hematologic diseases and tumors patients with post-chemotherapy bone marrow suppression, and lowest(16.9%, 13/77) in patients with no underlying diseases.Gram-negative bacterial infection was more common in SS children with underlying diseases(63.1%, 41/65), and was highest in the malignant hematologic diseases and tumors patients with post-chemotherapy bone marrow suppression(80.0%, 20/25). Gram-positive bacteria accounted for the highest proportion in the group without underlying disease(52.1%, 25/48). The incidence of multiple organ dysfunction syndrome(MODS) was the highest(95.6%, 43/45) in the malignant hematologic diseases and tumors patients with post-chemotherapy bone marrow suppression, and the lowest(59.7%, 46/77) in the group without underlying disease.Conclusion:Gram-negative bacteria is the most common pathogen in SS children with underlying diseases, especially in malignant hematologic diseases and tumors patients with post-chemotherapy bone marrow suppression, and with high mortality and incidence of MODS.Gram-positive bacteria is the most common pathogen for those without underlying diseases, with a relatively low mortality and incidence of MODS.
5.Prospective effects of protein and animal foods intake on age at menarche among Chinese girls
Chinese Journal of School Health 2021;42(4):493-496
Objective:
To investigate the prospective effects of the consumption of protein and animal foods before menarche on the age at menarche among Chinese girls.
Methods:
This paper was based on the data collected in the China Health and Nutrition Survey(CHNS) from 1997 to 2015. A total of 683 girls aged 6 and over who had completed information on age at menarche, height, weight, per capita annual household income, maternal education level and participated in at least one complete dietary survey within 1 to 4 years before menarche were included. Urban-rural stratified multivariable linear regression model was used to examine the effects of protein and animal foods intake before menarche on Chinese girls age at menarche in urban and rural areas.
Results:
After adjusted for total energy intake, body mass index standard deviation score and per capita annual household income, the consumption of meat before menarche was negatively associated with the age at menarche among rural Chinese girls(B=-0.003, P=0.00), but not among urban Chinese girls(B=0.002, P>0.05). Total protein, dairy, eggs and aquatic products intake before menarche were not associated with Chinese girls age at menarche in urban and rural areas(B=0.002, -0.001, 0.003, 0.000; 0.001, 0.001, -0.001, -0.003, P>0.05).
Conclusion
Higher intake of meat before menarche might lead to earlier menarche onset in rural Chinese girls. The consumption of total protein, dairy, eggs, and aquatic products before menarche did not affect the age at menarche in Chinese girls.
6.Influence of carbohydrate and fiber intakes on age at menarche in Chinese girls
CHEN Yue, DUAN Ruonan, GAO Wanke, LIU Xueting, DUAN Ruotong, CHENG Guo
Chinese Journal of School Health 2021;42(2):203-206
Objective:
To explore the relationship between premenarchal dietary carbohydrate and dietary fiber intakes and age at menarche in Chinese girls.
Methods:
Based on dietary and menarcheal information on 750 girls from the Chinese Health and Nutrition Survey, multivariate linear regression models and logistic models were used to analyze the influence of dietary carbohydrate and dietary fiber intakes before menarche onset and age at menarche. Carbohydrate intake was replaced by engergg ratio carbohydrate for a sensitivity analysis.
Results:
Adjusting for residence, per capita household income, body mass index standard deviation score, and energy intake, higher intake and higher energy ratio of carbohydrate were associated with later age at menarche(P<0.01). Compared to girls at the lowest tertile of carbohydrate intake level, those at the highest tertile had a 0.35 years(2.8%) delay in age at menarche, while 55% decreased[OR(95%CI)=0.45(0.30-0.69)]. Dietary fiber intake was not associated with age at menarche in any model(P>0.2).
Conclusion
Girls with higher premenarcheal carbohydrate intake experienced menarche later, while dietary fiber intake was not associated with age at menarche.
7.Studies of the norm of Karitane Parenting Confidence Scale(KPCS)among parents of infants in urban areas of China
Hongdi PAN ; Yue ZHANG ; He TANG ; Jinliuxing YANG ; Weiwei FENG ; Lijuan MU ; Dongmei YAN ; Jie SHAO ; Hong WANG ; Xueting GAO ; Ranke ZHU ; Guangwen HUANG ; Dongmei ZHAO ; Yan LUO ; Lanqiu LYU ; Jin SUN ; Jing YANG ; Shuangqin YAN ; Nianrong WANG ; Hong WANG
Chinese Journal of Preventive Medicine 2021;55(10):1209-1213
Objective:To establish the norm of the Chinese version of Karitane Parenting Confidence Scale (KPCS) in urban areas of China.Methods:From August to December 2017, the parents of 2 216 children (<36 months old) were selected from 15 cities (Beijing, Lianyungang, Hangzhou, Chengdu, Xi′an, Guangzhou, Changsha, Jinan, Guiyang, Ningbo, Dalian, Qinhuangdao, Maanshan, Chongqing and Wuhan) in 14 provinces by stratified random sampling. The general demographic characteristics and parents′ parenting confidence were collected by a self-made questionnaire and KPCS Chinese version. The percentile norm was established. P 3, P10 and P 25 were used as the criteria to define the degree of lack of parenting confidence. Results:The age of mothers was (30.67±4.29). The age of the father was (32.50±4.99) years old. There were 726 (32.76%), 759 (34.25%) and 731 (32.99%) infants in 6-12, 12-23 and 24-35 months old groups. The total scores of P 50, P 25, P 10 and P 3 of KPCS (Chinese version) of infant parents in urban areas in China were 41, 38, 33, and 29 respectively. When the scores of parents were 34-37, 30-33, and ≤ 29, they were judged as mild, moderate, and severe lack of parenting confidence. There was no significant difference in the Chinese version of KPCS between parents of different age groups and parents of different gender (χ2=3.53, P=0.171; χ2=1.41, P=0.236). Each factor score≤ P 3 is defined as the boundary score, and the corresponding boundary scores of "parenting" "support" and "competence" were 13, 9, and 5 respectively. Conclusion:The Chinese version of KPCS can be used to assess the parenting confidence of infants in urban areas of China. It can used as one of the bases for scientific and objective evaluation of the parenting status of families.
8.A prospective study on the associations between dietary intakes of energy and macronutrients before menarche and age at menarche among girls
Ruonan DUAN ; Wanke GAO ; Yue CHEN ; Tian QIAO ; Jing LI ; Xueting LIU ; Ping FENG ; Guo CHENG
Chinese Journal of Preventive Medicine 2021;55(10):1228-1231
Based on the data from China Health and Nutrition Survey (CHNS), 840 girls aged 6-15 years who had information about menarche and participated in dietary survey at least once within 1-5 years before onset of menarche between 1989 and 2015 were included in the study. The median age at baseline of the 840 participants was 10 (9, 11) years. The median age at menarche of the participants was 13 (12, 14) years. After adjusting for the age of birth, place of residence, body mass index Z-score, physical activity level and annual household income per capita, the average age of menarche was advanced by 0.036 (95% CI: -0.068, -0.004) years for every 10 g increase in daily fat intake before menarche. The average age at menarche was 0.008 (95% CI: -0.014, -0.001) years earlier for every 1% increase in the daily energy supply ratio of fat before menarche.
9.Studies of the norm of Karitane Parenting Confidence Scale(KPCS)among parents of infants in urban areas of China
Hongdi PAN ; Yue ZHANG ; He TANG ; Jinliuxing YANG ; Weiwei FENG ; Lijuan MU ; Dongmei YAN ; Jie SHAO ; Hong WANG ; Xueting GAO ; Ranke ZHU ; Guangwen HUANG ; Dongmei ZHAO ; Yan LUO ; Lanqiu LYU ; Jin SUN ; Jing YANG ; Shuangqin YAN ; Nianrong WANG ; Hong WANG
Chinese Journal of Preventive Medicine 2021;55(10):1209-1213
Objective:To establish the norm of the Chinese version of Karitane Parenting Confidence Scale (KPCS) in urban areas of China.Methods:From August to December 2017, the parents of 2 216 children (<36 months old) were selected from 15 cities (Beijing, Lianyungang, Hangzhou, Chengdu, Xi′an, Guangzhou, Changsha, Jinan, Guiyang, Ningbo, Dalian, Qinhuangdao, Maanshan, Chongqing and Wuhan) in 14 provinces by stratified random sampling. The general demographic characteristics and parents′ parenting confidence were collected by a self-made questionnaire and KPCS Chinese version. The percentile norm was established. P 3, P10 and P 25 were used as the criteria to define the degree of lack of parenting confidence. Results:The age of mothers was (30.67±4.29). The age of the father was (32.50±4.99) years old. There were 726 (32.76%), 759 (34.25%) and 731 (32.99%) infants in 6-12, 12-23 and 24-35 months old groups. The total scores of P 50, P 25, P 10 and P 3 of KPCS (Chinese version) of infant parents in urban areas in China were 41, 38, 33, and 29 respectively. When the scores of parents were 34-37, 30-33, and ≤ 29, they were judged as mild, moderate, and severe lack of parenting confidence. There was no significant difference in the Chinese version of KPCS between parents of different age groups and parents of different gender (χ2=3.53, P=0.171; χ2=1.41, P=0.236). Each factor score≤ P 3 is defined as the boundary score, and the corresponding boundary scores of "parenting" "support" and "competence" were 13, 9, and 5 respectively. Conclusion:The Chinese version of KPCS can be used to assess the parenting confidence of infants in urban areas of China. It can used as one of the bases for scientific and objective evaluation of the parenting status of families.
10.A prospective study on the associations between dietary intakes of energy and macronutrients before menarche and age at menarche among girls
Ruonan DUAN ; Wanke GAO ; Yue CHEN ; Tian QIAO ; Jing LI ; Xueting LIU ; Ping FENG ; Guo CHENG
Chinese Journal of Preventive Medicine 2021;55(10):1228-1231
Based on the data from China Health and Nutrition Survey (CHNS), 840 girls aged 6-15 years who had information about menarche and participated in dietary survey at least once within 1-5 years before onset of menarche between 1989 and 2015 were included in the study. The median age at baseline of the 840 participants was 10 (9, 11) years. The median age at menarche of the participants was 13 (12, 14) years. After adjusting for the age of birth, place of residence, body mass index Z-score, physical activity level and annual household income per capita, the average age of menarche was advanced by 0.036 (95% CI: -0.068, -0.004) years for every 10 g increase in daily fat intake before menarche. The average age at menarche was 0.008 (95% CI: -0.014, -0.001) years earlier for every 1% increase in the daily energy supply ratio of fat before menarche.


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