Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Objective To investigate the relationship between the risk perception and nursing working environment with the mental resilience in the emergency department nurses.Methods The convenience sam-pling method was adopted.A total of 577 emergency department nurses in 45 hospitals of Guangdong Province from October to November 2023 were selected as the respondents.The CD-RISC scale,nursing staff risk per-ception questionnaire and nursing work environment scale were used to conduct the survey.The multiple line-ar regression was adopted to analyze the influencing factors of mental resilience in the emergency department nurses.The Pearson correlation was adopted to analyze the correlation between the risk perception and nursing working environment with the mental resilience.Results The gender,age,specialist nurse or not,post,hospi-tal type and hospital level had the effect on the mental resilience in the emergency department nurses (P<0.05).The scores of mental resilience scale in 577 nurses were (86.07±15.95) points and the scoring rate was 68.86％;the scores of nursing staff risk perception questionnaire were (79.38±16.32) points and the scoring rate was 56.70％;the scores of the nursing work environment scale were (93.51±13.25) points and the scoring rate was 75.41％.The multiple linear regression analysis showed that the post was the influencing factor of mental resilience in the emergency department nurses.The results of Pearson correlation analysis showed that the nursing work environment was positively correlated with the mental resilience (r=0.476),and negatively correlated with the risk perception (r=-0.252).Conclusion The hospital nursing managers should pay attention to the influencing factors of mental resilience in the emergency department nurses and fo-cus on three major types of risks affecting physical function,time and occupational exposure of the emergency department nurses to improve the working environment of emergency nursing.

Objective To investigate the effect of esketamine on perioperative pain and depression in patients with thoracoscopic pulmonary nodule resection. Methods A total of 120 patients with selective thoracoscopic pulmonary nodule resection were randomly divided into low-dose esketamine group (group L), high-dose esketamine group (group H) and saline control group (group C), with 40 cases in each group. Before skin incisionafter anesthetic induction, 0.25 mg/kgesketamine, 0.50 mg/kg esketamine and the equivalent amount of saline were separately administered for patients in the three groups. Visual Analogue Scale (VAS) score for pain and the Self-rating Depression Scale (SDS) score were compared among the three groups at the time points of one day before surgery (T₀), one day after surgery (T₁), three days after surgery (T₂), and the day of discharge (T₃), and postoperative analgesia within 24 h and perioperative adverse reactions were also recorded. Results The VAS scores for rest and coughing at T₁ were significantly lower in group L and group H than group C (P < 0.05); compared with group C, the total press number of analgesic pump with in 24 h and effective press number were significantly decreased in group L and group H, and the dosage of sufentanil was also significantly decreased(P < 0.05). There were no significant differences in depression scores at different time points among the three groups (P>0.05). There were no significant differences in the incidence rates of nausea, vomiting, dizziness, hallucinations, and nightmares among the three groups (P>0.05). Conclusion Esketamine can effectively alleviate pain on the first day after operation and reduce the dosage of opioid analgesics without increasing the incidence of adverse reactions in patients with thoracoscopic pulmonary nodule resection; compared with 0.25 mg/kg esketamine, 0.50 mg/kg esketamine doesn't demonstrate better postoperative analgesia or improvement in perioperative depression.

Heme/metabolism* ; Cryoelectron Microscopy ; Membrane Transport Proteins ; Escherichia coli Proteins/metabolism*

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Alzheimer''s disease (AD) has brought to us huge medical and economic burdens, and so discovery of its therapeutic drugs is of great significance.In this paper, we utilized knowledge graph embedding (KGE) models to explore drug repurposing for AD on the publicly available drug repurposing knowledge graph (DRKG).Specifically, we applied four KGE models, namely TransE, DistMult, ComplEx, and RotatE, to learn the embedding vectors of entities and relations on DRKG.By using three classical knowledge graph evaluation metrics, we then evaluated and compared the performance of these models as well as the quality of the learned embedded vectors.Based on our results, we selected the RotatE model for link prediction and identified 16 drugs that might be repurposed for the treatment of AD.Previous studies have confirmed the potential therapeutic effects of 12 drugs against AD, i.e., glutathione, haloperidol, capsaicin, quercetin, estradiol, glucose, disulfire, adenosine, paroxetine, paclitaxel, glybride and amitriptyline.Our study demonstrates that drug repurposing based on KGE may provide new ideas and methods for AD drug discovery.Moreover, the RotatE model effectively integrates multi-source information of DRKG, enabling promising AD drug repurposing.The source code of this paper is available at https://github.com/LuYF-Lemon-love/AD-KGE.

【Objective】 To conduct a case-control study on precocious puberty as an example to introduce the establishment and design of the electronic Data capture and management platform using Research Electronic data Capture (REDCap) system and support the development of clinical research. 【Methods】 Based on the clinical REDCap system, the case-control research project of precocious puberty was created, the case report forms were designed, the user rights were set, and the data quality control rules were formulated. 【Results】 We established the electronic data capture and management platform for our research, which had 15 case report forms, to collect the data of the participants, including sociodemographic information, time for rest and activities, diet, exposure to environmental internal-secretion interfering-substances, physical examination and biochemical indicators. We conducted project management by setting up features such as user permissions and workgroups, and added data quality verification rules to control data quality. The data could be exported in various file formats for analysis and sharing. 【Conclusion】 The application of REDCap to establish the data capture and management platform of precocious puberty case-control study has promoted the efficient implementation of clinical research, which can be further popularized and applied to clinical researches in other fields.

Objective:To investigate the hepatitis B surface antigen (HBsAg) clearance condition and its predictive factors after treatment with nucleos(t)ide analogues to pegylated interferon-α add-on therapy in patients with chronic hepatitis B.Methods:Patients with chronic hepatitis B who visited the First Affiliated Hospital of Zhengzhou University from 2018~2019 were prospectively enrolled. HBsAg≤ 1500 IU/mL, hepatitis B e antigen-negative, HBV DNA undetectable, received antiviral treatment with nucleos(t)ide analogues for at least one year, and pegylated interferon-α add-on therapy for 48 weeks were included. The primary endpoint of study was to determine the proportion of HBsAg clearance at 72 weeks. Concurrently, the predictive factors for HBsAg clearance were analyzed. Quantitative and qualitative data were analyzed using a t-test or non-parametric test and a Fisher's exact test.Results:A total of 38 cases were included in this study, of which 13 cases obtained HBsAg clearance at 48 weeks of therapy and another six cases obtained HBsAg clearance throughout the extended treatment period of 72 weeks, accounting for 50.00% of all enrolled patients. There was a significant difference in HBsAg dynamics between the HBsAg clearance group and the non-clearance group (P < 0.05). Univariate logistic regression analysis showed that patients' age, baseline, 12-and 24-week HBsAg levels, and early HBsAg reduction were predictive factors for HBsAg clearance at 72 weeks of treatment. Multivariate logistic regression analysis showed that age (OR = 1.311; P = 0.016; 95% confidence interval: 1.051~1.635) and HBsAg levels at 24 weeks of treatment (OR = 4.481; P = 0.004; 95% confidence interval: 1.634~12.290) were independent predictors for HBsAg clearance.Conclusion:Hepatitis B e antigen-negative, nucleos(t)ide analogue treated, HBsAg ≤ 1500 IU/mL, and HBV DNA undetectable, peg-IFNα add-on treatment for 48 weeks could promote HBsAg clearance in patients with chronic hepatitis B. Six of the sixteen cases (37.50%) who did not obtain HBsAg clearance at week 48 did so with the course of therapy extended to week 72. Hence, the optimal individualized treatment strategy should be customized according to the predictors rather than the fixed 48-week course. Age (≤ 38), baseline HBsAg level (≤2.86 log 10IU/ml), HBsAg level at 24 weeks (≤ 0.92 log 10IU/ml), and 12-week HBsAg decrease from baseline (≥ 0.67 log 10IU/ml) indicate that patients are highly likely to obtain HBsAg clearance at the 72 weeks of combination therapy, in which the combined indicator based on HBsAg level ≤0.92 log 10IU/ml at 24 weeks will identify 85.0% to 100.0% of patients with HBsAg clearance.

Objective:To investigate the relationship between the level of Apelin-13 and coronary artery lesion (CAL) in patients with Kawasaki disease (KD), and assess the predictive value of Apelin-13 for CAL in acute phase of KD.Methods:A total of 240 children with KD treated in Chengdu Women and Children′s Central Hospital from September 2017 to October 2019 were recruited, and were divided into KD with CAL (KD-CAL) group and KD without CAL (KD-NCAL) group.Thirty children with acute upper respiratory infection and 30 healthy children were recruited into the febrile control group and the healthy control group, respectively.Blood routine and serum levels of albumin, C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and Apelin-13 were mea-sured in KD children prior to intravenous gamma globulin injection and after the diagnosis of children in the febrile control group and physical examination of children in the healthy control group.The clinical data of children in each group were compared, and the risk factors of KD complicated with CAL and the predictive value of Apelin-13 were determined by using receiver operating characteristic (ROC) curve and multiple Logistic regression analysis. Results:Apelin-13 and hemoglobin in children with KD were significantly decreased compared with those in the healthy control group and fever control group (all P<0.001). However, white blood cell(WBC) count, platelet count, CRP and NT-proBNP in KD group were significantly increased compared with those in the healthy control group and fever control group (all P<0.001). Serum albumin in KD children was significantly lower than that in the healthy control group ( P=0.004), and there was no difference when compared with the fever control group ( P=0.485). Apelin-13 and hemoglobin were significantly decreased in KD-CAL group compared with KD-NCAL group ( t=10.102, P<0.001; t=2.034, P=0.043), while NT-proBNP and CRP were significantly increased ( t=5.982, 3.728, all P<0.001). Multiple logistic regression analysis showed that Apelin-13 and NT-proBNP were independent predictors of CAL in KD.The ROC curve analysis showed that the cut-off value of Apelin-13 for predicting CAL was 2.99 μg/L, with an area under the curve (AUC) of 0.869 (95% CI: 0.820-0.909), sensitivity of 77.78% and specificity of 88.67%.While NT-proBNP cutoff value of 822 ng/L yielded sensitivity of 57.78% and specificity of 84.62% for predicting CAL with an AUC of 0.718(95% CI: 0.656-0.774). Conclusions:Apelin-13 plays a protective role in KD complicated with CAL, and could be used to predict CAL in the acute phase of KD.

Objective:To investigate the application value of Overlap guiding tube (OGT) in Overlap esophagojejunostomy of laparoscopic total gastrectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 5 patients with gastric cancer who were admitted to Nanfang Hospital of Southern Medical University from June to July in 2021 were collected. There were 3 males and 2 females, aged from 48 to 61 years, with a median age of 54 years. Patients underwent laparoscopic total gastrectomy combined with OGT-assisted Overlap esophagojejunostomy. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted by outpatient examination and telephone interview to detect postoperative anastomotic stenosis and esophageal reflux up to September 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR) or M(range). Count data were represented as absolute numbers. Results:(1) Surgical situations: 5 patients underwent laparoscopic total gastrectomy combined with OGT-assisted Overlap esophagojejunostomy and D 2 lymph node dissection success-fully, achieving R 0 resection. There was no combined organ resection, intraoperative conversion to laparotomy or combined thoracotomy. There was no intraoperative conversion to other esophagoje-junostomy method either. The tumor diameter, length of surgical incision, the number of lymph nodes dissected, time of esophagojejunal anastomosis, time of digestive reconstruction, operation time, volume of intraoperative blood loss of 5 patients were 3.0(2.8)cm, 5.0(2.0)cm, 47.0(21.0), 21.0(5.0)minutes, 62.0(23.0)minutes, 295.0(75.0)minutes, and 50.0(60.0)mL, respectively. The anvil fork of linear stapler was successfully inserted into esophageal lumen by once operation in 4 cases of 5 patients and by twice operation in 1 case to complete the esophagojejunostomy. (2) Post-operative situations: the time to first out-of-bed activities, time to postoperative first anal flatus, time to postoperative initial liquid diet intake, time to postoperative initial semi-liquid diet intake, time to abdominal drainage tube removal, duration of postoperative hospital stay of 5 patients were 2.0(1.0)days, 3.0(2.0)days, 4.0(3.0)days, 6.0(3.0)days, 7.0(4.0)days, and 9.0(6.0)days, respectively. Results of postoperative pathological examination of 5 patients showed gastric adenocar-cinoma in all the 5 patients, with the TNM staging as stage pT2-4aN0M0. The esophageal surgical margin was negative in all cases, and the length of proximal margin from esophagus was 5.0(4.0)cm. None of the 5 patients developed anastomotic leakage, anastomotic bleeding or anastomotic stenosis. Two cases with mild pneumonia (Clavien-Dindo grade Ⅱ) were cured by conservative treatment such as anti-infection and expectoration promotion. There was no unplanned secondary surgery or perioperative death occurred to the 5 patients. (3) Follow-up: 5 patients were followed up for 3 months. None of the 5 patients developed anastomotic stenosis or esophageal reflux during the follow-up. Conclusion:OGT-assisted Overlap esophagojejunostomy of laparoscopic total gas-trectomy is safe and feasible, with good short-term effects.