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 examine the causal relationship between ulcerative colitis (UC) and pancreatitis, to provide basis for early screening of pancreatitis among UC patients. Methods: Genomic data of UC were obtained from 47 745 European individuals pooled by the International Inflammatory Bowel Disease Genetics Consortium, including 156 116 single nucleotide polymorphism (SNP), and genomic data of pancreatitis were obtained from 198 166 European individuals pooled from FinnGen, including 16 380 428 SNPs. Mendelian randomization (MR) analysis was performed using the inverse variance weighted (IVW) method with 72 UC-associated SNPs as instrumental variables and pancreatitis as the study outcome. The heterogeneity was assessed using Cochran Q test, the horizontal pleiotropy was assessed using MR-Egger regression, MR-PRESSO was performed with the exclusion of outliers, and effect of individual SNP on the results was tested with the leave-one-out method. Results: MR analysis results showed that patients with genetically predicted UC had an increased risk of pancreatitis relative to those without UC (OR=1.076, 95%CI: 1.019-1.136, P<0.05). Cochran Q test showed no heterogeneity (P>0.05), and MR-Egger regression did not reveal horizontal pleiotropy of instrumental variables (P>0.05). The MR analysis results were robust after removing SNP one by one. Conclusions Genetically predicted UC is associated with an increased risk of pancreatitis. The screening for pancreatitis risk should be enhanced in patients with UC.

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.

Objective To evaluate and summarize the evidence related to the prevention of parenteral nutritional support complications in inpatients,and to provide an evidence-based basis for guiding healthcare professionals to prevent parenteral nutritional support complications in a scientific and standardized manner.Methods Computerized search was conducted in UpToDate,BMJ Best Clinical Practice,Centre for Evidence-Based Health Care database of the Joanna Briggs Institute in Australia,Ontario Registered Nurses Association website in Canada,National Institute for Health and Clinical Excellence website in the United Kingdom,Scottish Intercollegiate Guidelines Network,Guidelines International,New Zealand Guidelines Collaborative,American Society for Parenteral and Enteral Nutrition website,European Society for Clinical Nutrition and Metabolism Society website,International Practice Guidelines Registry Platform China Clinical Guidelines Repository,Medical Pulse,PubMed,Cochrane Library,Web of Science,CINAHL,Embase,China Biomedical Literature Database,CNKI,Wanfang Database,etc.The search period was from the time of database construction to October 2023.After literature screening and quality evaluation,the evidence extraction and integration were carried out.Results A total of 16 papers were included,including 3 clinical decision-making,1 evidence summary,4 guidelines,6 expert consensuses,and 2 systematic evaluations.27 pieces of best evidence were extracted from 3 areas,namely metabolic complications,mechanical complications,and infectious complications.Conclusion This study summarized the evidence related to the prevention and management of complications of parenteral nutrition support in adult inpatients,aiming to provide an evidence-based basis for healthcare professionals to develop scientific and standardized measures for the prevention and management of complications of parenteral nutrition support.

Objective:To explore the effect and safety of local spraying tranexamic acid after thyroidectomy.Methods:Randomized double-blind placebo-controlled study method was used. Sixty-four patients underwent scheduled thyroidectomy from December 2022 to August 2023 in Baotou Cancer Hospital were selected. The patients were divided into tranexamic acid group and control group by random digits table method with 32 cases each. Before closing the wound during surgery, 16 ml of tranexamic acid injection with concentration of 25 mg/ml was used to wash the wound and 1 ml of tranexamic acid injection (tranexamic acid 100 mg) used to locally spray in tranexamic acid group; 16 ml of the sterile water for injection was used to wash the wound and 1 ml of sterile water for injection was used locally spray in control group, and then the drainage tube was clipped for 20 min. The neck drainage volume on the first to fourth day after surgery and complication were recorded; the C-reactive protein level before and after surgery was detected.Results:Two patients in each group withdrew from the study midway. The drainage volume on the first, second and third day and total drainage volume in tranexamic acid group were significantly lower than those in control group: (29.10 ± 8.04) ml vs. (38.50 ± 8.67) ml, (18.00 ± 7.33) ml vs. (27.20 ± 10.66) ml, (10.70 ± 5.75) ml vs. (14.60 ± 6.83) ml and (69.20 ± 24.48) ml vs. (96.70 ± 31.90) ml, and there was statistical difference ( P<0.01); there was no statistical difference in the drainage volume on the fourth day after surgery between two groups ( P>0.05). There was no statistical difference in C-reactive protein before and after surgery between two groups ( P>0.05). There was 1 case of fever (body temperature 37.5 ℃) in the control group, and there were no complications such as intermuscular thrombosis, venous thrombosis, incision infection and delayed wound healing in both groups. Conclusions:Local application of tranexamic acid after thyroidectomy can reduce postoperative drainage volume and does not increase the risk of thrombosis, infection and delayed healing.

Objective:To explore the rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by bedside diagnostic bronchoscopy, so as to start effective anti-infection treatment before the results of macrogenome next generation sequencing (mNGS) test. Methods:The clinical data of three patients with severe Chlamydophila psittaci pneumonia who were successfully treated in the First Affiliated Hospital of Xinjiang Medical University, the First People's Hospital of Aksu District, and the First Division Hospital of Xinjiang Production and Construction Corps from October 2020 to June 2021 were retrospectively analyzed, including the rapid assessment of early pathogens by bedside diagnostic bronchoscopy and the use of antibiotics to start anti-infection treatment. These patients were successfully treated. Results:The three patients were male, aged 63, 45 and 58 years old, respectively. Before the onset of the penumonia, they had a clear medical history of bird exposure. The clinical manifestations mainly included fever, dry cough, shortness of breath and dyspnea. One case had abdominal pain and lethargy. The results of laboratory examination indicated that the peripheral blood white blood cell count (WBC) of two patients were high [(10.2-11.9)×10 9/L], the percentage of neutrophils increased (85.2%-94.6%) and the percentage of lymphocytes decreased (3.2%-7.7%) in all 3 patients after admission to hospital and entering into intensive care unit (ICU). The procalcitonin (PCT) of 3 patients increased after admission, and still increased when entering ICU (0.3-4.8 ng/L), so did C-reactive protein (CRP, 58.0-162.0 mg/L) and erythrocyte sedimentation rate (ESR, 36.0-90.0 mm/1 h). After admission, serum alanine transaminase (ALT) increased in 2 cases (136.7 U/L, 220.5 U/L), so did aspartate transaminase (AST) in 2 cases (249.6 U/L, 164.2 U/L). ALT (162.2-267.9 U/L) and AST (189.8-223.2 U/L) increased in 3 patients when they entered ICU. The level of serum creatinine (SCr) of 3 patients were normal after admission and entering ICU. The chest computed tomography (CT) findings of 3 patients were acute interstitial pneumonia, bronchopneumonia and lung consolidation, of which 2 cases were accompanied by a small amount of pleural effusion, and 1 case was accompanied by more regular small air sacs. Multiple lung lobes were involved, but mainly one lung lobe. The oxygenation index (PaO 2/FiO 2) of the 3 patients admitting to ICU were 100.0, 57.5 and 105.4 mmHg (1 mmHg ≈ 0.133 kPa), respectively, which met with the diagnostic criteria of moderate and severe acute respiratory distress syndrome (ARDS). All three patients received endotracheal intubation and mechanical ventilation. Under the bedside bronchoscope, the bronchial mucosa of 3 patients were obviously congested and edematous, without purulent secretion, and there was 1 case with mucosal hemorrhage. Three patients underwent bedside diagnostic bronchoscopy, and the evaluation result of the pathogen was that it might be atypical pathogen infection, so they were given moxifloxacin, cisromet and doxycycline intravenously, respectively, and combined with carbapenem antibiotics intravenously. After 3 days, the detection results of mNGS in bronchoalveolar lavage fluid (BALF) showed that only Chlamydia psittaci was infected. At this time, the condition was significantly improved, and PaO 2/FiO 2 was significantly increased. Therefore, the antibiotic treatment scheme remained unchanged, and mNGS only served to verify the initial diagnosis. Two patients were extubated on the 7th and 12th day of admission to the ICU, respectively, while one patient was extubated on the 16th day of admission to the ICU due to nosocomial infection. All 3 patients were transferred to the respiratory ward after the condition was stable. Conclusion:The bedside diagnostic bronchoscopy based on clinical characteristics is conducive to not only the rapid assessment of the early pathogens of severe Chlamydia psittaci pneumonia, but also effective anti-infection treatment before the returning of mNGS test results, which can make up for the lag and uncertainty of the mNGS test results.

The use of light energy to drive carbon dioxide (CO₂) reduction for production of chemicals is of great significance for relieving environmental pressure and solving energy crisis. Photocapture, photoelectricity conversion and CO₂ fixation are the key factors affecting the efficiency of photosynthesis, and thus also affect the efficiency of CO₂ utilization. To solve the above problems, this review systematically summarizes the construction, optimization and application of light-driven hybrid system from the perspective of combining biochemistry and metabolic engineering. We introduce the latest research progress of light-driven CO₂ reduction for biosynthesis of chemicals from three aspects: enzyme hybrid system, biological hybrid system and application of these hybrid system. In the aspect of enzyme hybrid system, many strategies were adopted such as improving enzyme catalytic activity and enhancing enzyme stability. In the aspect of biological hybrid system, many methods were used including enhancing biological light harvesting capacity, optimizing reducing power supply and improving energy regeneration. In terms of the applications, hybrid systems have been used in the production of one-carbon compounds, biofuels and biofoods. Finally, the future development direction of artificial photosynthetic system is prospected from the aspects of nanomaterials (including organic and inorganic materials) and biocatalysts (including enzymes and microorganisms).
Carbon Dioxide/metabolism* ; Photosynthesis ; Metabolic Engineering

Objective : o evaluate the association between Crohn's disease (CD) and frailty using a Mendelian randomization (MR) approach, so as to provide the evidence for prevention and control strategies. Methods: Genetic association data for CD were collected through the International Inflammatory Bowel Disease Genetics Consortium, with 20 883 samples and 12 276 506 single nucleotide polymorphism (SNP), and genetic association data for frailty were collected through a meta-analysis including 175 226 samples and 7 589 717 SNPs. A forward MR analysis was performed using the inverse-variance weighted (IVW) method with 37 CD-associated SNPs as instrumental variables, and frailty as the study outcome, and a reverse MR analysis was performed with 13 frailty-associated SNPs as instrumental variables and CD as the study outcome. The heterogeneity was assessed using the Cochran's Q test, and the horizontal pleiotropy was assessed using the MR-PRESSO global test and MR-Egger regression. In addition, the robustness of the results was verified with the leave-one-out. Results: Forward MR analysis results showed that patients with genetically predicted CD had an increased risk of frailty index relative to those without CD (β=0.018, 95%CI: 0.011-0.026, P<0.05). Cochran's Q test detected no heterogeneity (P>0.05), and neither the MR-PRESSO test nor the MR-Egger regression revealed horizontal pleiotropy of instrumental variables (both P>0.05). Leave-one-out analysis showed robustness of the MR analysis results. Reverse MR analysis showed no association between frailty index and the risk of CD (OR=0.740, 95%CI: 0.206-2.661, P>0.05). Conclusions Genetically predicted CD is associated with an increased risk of frailty. It is suggested that screening and prevention of frailty should be reinforced among CD patients.

Background: and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. Methods: This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. Results: Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). Conclusion In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.

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