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.

Objective:To investigate the causal relationship between plasma proteins and spontaneous abor-tion using a two-sample Mendelian randomization method.Methods:Using genome-wide association study(GWAS)data from an Icelandic population as an exposure factor and spontaneous abortion data from the Finn-ish Genetic Research Project(FinnGen)as an outcome,the causal relationship between plasma proteins and the risk of developing spontaneous abortion was analyzed using a Mendelian randomization(MR)study.The inverse variance weighting(IVW)method was used as the primary study method,with MR-Egger,weighted median and weighted mode complementing the results;and sensitivity analyses were performed using Cochrane's Q test,MR-Egger intercept testand leave-one-out method to validate the reliability of the data.Results:Seven plasma proteins were identified as potentially correlated with the risk of spontaneous abortion of which fucosyltransferase 10(FUT10)(OR 0.955,95％CI 0.915-0.996,P=0.034),plexin B2(PLXNB2)(OR 0.947,95％CI 0.902-0.995,P=0.030),and interleukin-11 receptor alpha(IL-11Rα)(OR0.905,95％CI 0.848-0.966,P=0.003)were associ-ated with a reduced risk of SA development,while plasma proteins soluble L-selectin(SL-selectin)(OR 1.076,95％CI 1.021-1.134,P=0.006),Cripto protein(OR 1.039,95％CI 1.008-1.071,P=0.012),dendritic cell-specif-ic intercellular adhesion molecule 3-grabbing non-integrin(DC-SIGN)(OR 1.051,95％CI 1.022-1.082,P=0.001),and protein Z-dependent protease inhibitor(ZPI)(OR 1.035,95％CI 1.001-1.071,P=0.045)levels were positively associated with the risk of developing SA.No heterogeneity or horizontal pleiotropy was detected(Co-chrane's Q test and MR-Egger intercept test,P＞0.05),and leave-one-out analysis showed that there were no individual single-nucleotide polymorphisms that had a large impact on the overall data.Conclusions:This Mende-lian randomization analyses confirmed the causal relationship between multiple plasma proteins and spontaneous abortion,which is potentially clinically valuable for studying the correlation between plasma proteins and spontane-ous abortion.

Objective:To investigate the causal relationship between plasma proteins and spontaneous abor-tion using a two-sample Mendelian randomization method.Methods:Using genome-wide association study(GWAS)data from an Icelandic population as an exposure factor and spontaneous abortion data from the Finn-ish Genetic Research Project(FinnGen)as an outcome,the causal relationship between plasma proteins and the risk of developing spontaneous abortion was analyzed using a Mendelian randomization(MR)study.The inverse variance weighting(IVW)method was used as the primary study method,with MR-Egger,weighted median and weighted mode complementing the results;and sensitivity analyses were performed using Cochrane's Q test,MR-Egger intercept testand leave-one-out method to validate the reliability of the data.Results:Seven plasma proteins were identified as potentially correlated with the risk of spontaneous abortion of which fucosyltransferase 10(FUT10)(OR 0.955,95％CI 0.915-0.996,P=0.034),plexin B2(PLXNB2)(OR 0.947,95％CI 0.902-0.995,P=0.030),and interleukin-11 receptor alpha(IL-11Rα)(OR0.905,95％CI 0.848-0.966,P=0.003)were associ-ated with a reduced risk of SA development,while plasma proteins soluble L-selectin(SL-selectin)(OR 1.076,95％CI 1.021-1.134,P=0.006),Cripto protein(OR 1.039,95％CI 1.008-1.071,P=0.012),dendritic cell-specif-ic intercellular adhesion molecule 3-grabbing non-integrin(DC-SIGN)(OR 1.051,95％CI 1.022-1.082,P=0.001),and protein Z-dependent protease inhibitor(ZPI)(OR 1.035,95％CI 1.001-1.071,P=0.045)levels were positively associated with the risk of developing SA.No heterogeneity or horizontal pleiotropy was detected(Co-chrane's Q test and MR-Egger intercept test,P＞0.05),and leave-one-out analysis showed that there were no individual single-nucleotide polymorphisms that had a large impact on the overall data.Conclusions:This Mende-lian randomization analyses confirmed the causal relationship between multiple plasma proteins and spontaneous abortion,which is potentially clinically valuable for studying the correlation between plasma proteins and spontane-ous abortion.

To evaluate the correlation between ultrasound ossification ratio(OR) and exercise intensity among adolescents.

Objective To analyze the real experiences of patients with inflammatory bowel disease(IBD)during dietary restrictions,providing references for healthcare personnel to guide patients in standardizing dietary restriction behaviors.Methods Purposeful sampling was employed to select 14 patients with IBD who were treated at a tertiary A hospital in Shanghai between October 2022 and February 2023 for semi-structured in-depth interviews.Data were analyzed using the Colaizzi's 7-step method in phenomenological research.Results 4 themes and 13 sub-themes were extracted.Theme 1:facing multiple physiological challenges(hunger,nutritional imbalance,fatigue and muscle atrophy).Theme 2:experiencing negative psychological disturbances(craving and struggle for gourmet food,diminished zest for life and increased anxiety,feeling embarrassed during social activities).Theme 3:adopting various coping strategies(self-adjustment and adaptation to dietary restrictions,satisfying oral desires through various avenues,seeking knowledge and guidance on nutrition).Theme 4:gaining more growth and support(improved symptom and quality of life,enhanced awareness of dietary health,improved ability to manage diet,receiving support from peers and family).Conclusion The experience of dietary restrictions in IBD patients is complex and varied.Nursing staff should prioritize nutritional risk screening for IBD patients,pay attention to their mental health,provide patients with scientific and personalized dietary guidance,and strengthen social and family support to assist patients in better self-management of their diet.

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective: To investigate the snoring status and related family factors of children from 3 to 14 years old in Beijing. Methods: From May to July, 2015, data of children from 3 to 14 years old were obtained from a status survey from 7 districts(Xicheng, Chaoyang, Changping, Shunyi, Fangshan, Huairou and Mentougou) in Beijing. A total of 11 420 children from 25 primary and middle schools were randomly selected. Pediatric Sleep Questionnaire (PSQ) and a self-administered questionnaire were carried out for the adopted children. Self-administered questionnaire included the snoring related family factors. Logistic regression was used to estimate the odd ratio(OR) with 95% confidence intervals for variables. Results: A total of 9 198 children meet the inclusion criteria and are analyzed in the study, of whom 901 (9.80%) were found with snoring behavior. The incidence of boys is higher than girls. Obese children take higher risk of snoring. Compared with younger children (≤6 years old), older children (≥12 years old) have a significantly lower risk of snoring (OR=0.464, 95%CI 0.368-0.585). There is no statistical association between full-term infants, infant feeding pattern, parental cigarette smoking and child snoring.The children with family history of snoring have a significantly higher risk of snoring occurrence. The educational background of mother is statistically related to children snoring (OR=1.241, 95%CI 1.058-1.457). Conclusions The incidence of children snoring in Beijing is 9.80%, male gender, obesity, and young age are all risk factors for children snoring. There is a significantly statistical relationship between snoring and related family factors, such as family snoring history and education experience.

Objective: To investigate the sleep quality of children in Beijing and to analyze the related factors. Methods: The data were collected from the survey of 3-14 years old children in 7 urban districts of Beijing in 2015. By using multi-stage stratified cluster random sampling method, 26 kindergartens and primary and secondary schools in 7 districts and counties, including Xicheng, Chaoyang, Changping, Shunyi, Fangshan, Huairou and Mentougou, were randomly selected, with a total of 11 420 children. Children′s sleep status was investigated with Children′s Sleep Questionnaire (PSQ), and the proportion of children with sleep quality problems when the PSQ score was greater than 7. Various sleep related factors were investigated with self-made questionnaire. A multilevel model was used to analyze the relationship between PSQ score and related factors. Results: The average PSQ score of the children was 3.60±2.69. The proportion of children with sleep quality problems was 8.87%(816/9 198). Multilevel model analysis showed that the younger the children, the higher the PSQ score (<6 years old vs. 6~12 years old vs. >12 years old: 3.94±2.58 vs. 3.58±2.66 vs. 3.30±2.84, F=33.015, P<0.001); male PSQ score higher than female (3.89±2.75 vs. 3.30±2.60, t=10.560, P<0.001); and snoring, obesity, father/mother snoring, playing games before bed, surfing the internet, eating and other factors were statistically related to PSQ. Conclusions Sleep quality of children in Beijing should not be neglected, especially preschool children with high PSQ scores. Parents should pay attention to children′s snoring problems and try to reduce some pre-sleep behaviors that may affect sleep quality.

OBJECTIVE： To investigate the characteristics and regularity of gestational （including perinatal period） adverse drug reactions （ADR） in Sichuan province， and to provide evidence for ensuring the safety and effectiveness of drug use in clinic. METHODS： Gestational ADR reported to Sichuan provincial ADR monitoring center from Nov. 2016 to Nov. 2017 were statistically analyzed in respects of report source， personnel distribution， general information of patients， route of administration， drug types and main drugs， involved system/organ， grading and outcome， etc. RESULTS： A total of 1 309 gestational ADR cases   （1 340 case time） were collected， in which 1 305 were from medical institutions， 3 from enterprises and 1 from manufacturer. There were 986 physicians， 188 nurses， 133 pharmacists and 2 commissioners for drug safety. 859 cases （65.62％） were 21-30 years old， accounting for the largest proportion. 867 case time were caused by intravenous administration （64.70％）. ADR-inducing drug types mainly included reproductive system drugs （491 case time， 36.64％）， antimicrobial drugs （479 case time， 35.75％） and blood system drugs （110 case time， 8.21％）. Main of them were Carboprost tromethamine injection （187 case time， 13.96％）， Cefazolin sodium for injection （122 case time， 9.10％） and Oxytocin injection （105 case time， 7.84％）. ADR mainly involved skin and its appendants （517 case time， 33.95％）， gastrointestinal system （387 case time， 25.41％）， whole body （175 case time， 11.49％）.  In 1 309 gestational ADR， 1 251 cases （95.57％） were general ADR； 58 cases （4.43％） were severe ADR， including 14 life-threatening cases， 7 extended hospital stay and 37 others； 592 （45.22％） patients improved， 716 （54.70％） recovered and 1 （0.08％） did not improve. CONCLUSIONS： In clinical practice， it is necessary to strengthen the monitoring of drug use in patients during gestational， especially monitor ADR of uterine contraction drugs and antimicrobial drugs during gestational， use drug cautiously and promote clinical medication safety in gestational patients.

Objective: To investigate the snoring status of school-aged children in Beijing and explore the association of snoring and academic performance. Methods: A total of 7 925 children aged from 6 to 14 were selected from 15 primary and middle schools at 7 districts (Xicheng, Chaoyang, Changping, Shunyi, Fangshan, Huairou and Mentougou) in Beijing in 2015, using multi-stage stratified cluster random sampling method. The recruited children were asked to complete the Pediatric Sleep Questionnaire (PSQ) and a questionnaire related to sleep behavior. The multiplelogistic regression was used to analyze the association of snoring and academic performance. Results: A total of 794 (12.44%) children showed a decline in academic performance among 6 383 eligible respondentsfor data analysis. 580 (9.08%) children with snoring was identified, of which 333 and 247 were in frequency of 1-2 times per week and frequency of ≥3 times per week, respectively; 357, 170 and 53 were in snoring grade Ⅰ, grade Ⅱ and grade Ⅲ, respectively. Compared with the children without snoring, the OR (95%CI) for children with 1-2 times per week and ≥3 times per week was 1.363 (1.000-1.857) and 1.605 (1.135-2.269), respectively; and the OR (95%CI) for children with grade Ⅰ, grade Ⅱ and grade Ⅲ of snoring was 1.226 (0.893-1.683), 1.595 (1.062-2.397) and 2.31 (1.17-4.565), respectively. Conclusion There is a statistical relationship between snoring and the decline of academic performance. The decline of academic performance positively associated with increased frequency and grade of snoring.