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 establish the normal reference value of the left ventricular remodeling index（RI）in healthy adults，and to evaluate the phenotypes of RI in various left ventricular geometries and its relationship with left ventricular systolic and diastolic functions in asymptomatic hypertensive patients.Methods:A retrospective study design was employed，906 healthy Han Chinese volunteers were selected as the control group from the multicenter study "Echocardiographic Measurements in Normal Chinese Adults"（EMINCA），which was conducted in 2012. The normal reference range of left ventricular RI was established based on the 95% CI（ xˉ ± 1.96 s）. Statistical analyses were conducted to evaluate differences in RI across age groups and between genders. A total of 340 asymptomatic hypertensive patients in the Department of Health Management，Sichuan Provincial People's Hospital from July 2023 to March 2024 were prospectively included as the hypertension group. Conventional echocardiography and two-dimensional speckle tracking imaging were used to assess left ventricular structure and function. Parameters such as left ventricular mass index（LVMI），RI，relative wall thickness（RWT），the ratio of early diastolic mitral inflow velocity to the average early diastolic mitral annular velocity（E/e'），and the ratio of early diastolic to late diastolic mitral inflow velocities（E/A）were calculated. Differences of these parameters between the hypertension group and the healthy control group were compared. The hypertension group was stratified into 3 subgroups based on left ventricular posterior wall thickness at end-diastole（LVPWd）and RI：the non-LV hypertrophy group，the left ventricular hypertrophy with normal RI group，and the left ventricular hypertrophy with low RI group. Relevant parameters were compared among these subgroups，and the statistical significance of the differences was analyzed. Pearson correlation analysis and multiple linear regression analysis were performed to explore the relationships between left ventricular RI and GLS，LVEF，the average mitral annular peak systolic velocity（s'），e'，E/e'，E/A. Results:In the healthy control group，RI showed a declining trend with increasing age in both sexes. Furthermore，the RI was significantly higher in the female group compared to the male group（ P<0.001）. Compared with the healthy control group，LVMI and E/e' increased while RI，e' and s' decreased in the hypertension group（all P < 0.001）. Among the 3 subgroups of the hypertension group，compared with the other two groups，LVMI and Ｅ/e' increased while absolute GLS and s' reduced in the left ventricular hypertrophy with low RI subgroup（all P <0.001）. Pearson correlation analysis revealed that RI was negatively correlated with GLS and E/e'（ r=-0.457，-0.281；all P < 0.001），and positively correlated with LVEF，e'，s' and E/A（ r=0.229，0.394，0.150，0.172；all P < 0.05）. Multivariate linear regression analysis demonstrated that left ventricular RI was independently associated with GLS，LVEF，e'，s'，E/e' and E/A. Conclusions:The normal reference range of left ventricular RI tends to decrease with age and is typically higher in females than in males. In asymptomatic patients with primary hypertension，RI，systolic and diastolic functions of the left ventricular are lower，while LVMI is higher. Among these patients，functional impairment is more pronounced in patients with left ventricular hypertrophy and reduced RI. This indicates that left ventricular RI may offer an imaging basis for further classification and stratification of structural and functional abnormalities in the left ventricle of asymptomatic hypertensive patients.

Objective:To establish the normal reference value of the left ventricular remodeling index（RI）in healthy adults，and to evaluate the phenotypes of RI in various left ventricular geometries and its relationship with left ventricular systolic and diastolic functions in asymptomatic hypertensive patients.Methods:A retrospective study design was employed，906 healthy Han Chinese volunteers were selected as the control group from the multicenter study "Echocardiographic Measurements in Normal Chinese Adults"（EMINCA），which was conducted in 2012. The normal reference range of left ventricular RI was established based on the 95% CI（ xˉ ± 1.96 s）. Statistical analyses were conducted to evaluate differences in RI across age groups and between genders. A total of 340 asymptomatic hypertensive patients in the Department of Health Management，Sichuan Provincial People's Hospital from July 2023 to March 2024 were prospectively included as the hypertension group. Conventional echocardiography and two-dimensional speckle tracking imaging were used to assess left ventricular structure and function. Parameters such as left ventricular mass index（LVMI），RI，relative wall thickness（RWT），the ratio of early diastolic mitral inflow velocity to the average early diastolic mitral annular velocity（E/e'），and the ratio of early diastolic to late diastolic mitral inflow velocities（E/A）were calculated. Differences of these parameters between the hypertension group and the healthy control group were compared. The hypertension group was stratified into 3 subgroups based on left ventricular posterior wall thickness at end-diastole（LVPWd）and RI：the non-LV hypertrophy group，the left ventricular hypertrophy with normal RI group，and the left ventricular hypertrophy with low RI group. Relevant parameters were compared among these subgroups，and the statistical significance of the differences was analyzed. Pearson correlation analysis and multiple linear regression analysis were performed to explore the relationships between left ventricular RI and GLS，LVEF，the average mitral annular peak systolic velocity（s'），e'，E/e'，E/A. Results:In the healthy control group，RI showed a declining trend with increasing age in both sexes. Furthermore，the RI was significantly higher in the female group compared to the male group（ P<0.001）. Compared with the healthy control group，LVMI and E/e' increased while RI，e' and s' decreased in the hypertension group（all P < 0.001）. Among the 3 subgroups of the hypertension group，compared with the other two groups，LVMI and Ｅ/e' increased while absolute GLS and s' reduced in the left ventricular hypertrophy with low RI subgroup（all P <0.001）. Pearson correlation analysis revealed that RI was negatively correlated with GLS and E/e'（ r=-0.457，-0.281；all P < 0.001），and positively correlated with LVEF，e'，s' and E/A（ r=0.229，0.394，0.150，0.172；all P < 0.05）. Multivariate linear regression analysis demonstrated that left ventricular RI was independently associated with GLS，LVEF，e'，s'，E/e' and E/A. Conclusions:The normal reference range of left ventricular RI tends to decrease with age and is typically higher in females than in males. In asymptomatic patients with primary hypertension，RI，systolic and diastolic functions of the left ventricular are lower，while LVMI is higher. Among these patients，functional impairment is more pronounced in patients with left ventricular hypertrophy and reduced RI. This indicates that left ventricular RI may offer an imaging basis for further classification and stratification of structural and functional abnormalities in the left ventricle of asymptomatic hypertensive patients.

Objective:To investigate the diagnostic performance of CT-derived fractional flow reserve (CT-FFR) derived from standard images (STD), images processed by first-generation (SSF1) and second-generation (SSF2) whole-heart motion correction algorithm, respectively.Methods:Patients who underwent both coronary CT angiography (CCTA) and invasive coronary angiography (ICA) with FFR examination within 3 months in Shanghai General Hospital, Shanghai Jiao Tong Univerisity School of Medicine from January 2020 to December 2022 were screened in this retrospective study. Totally of 121 patients (134 lesions) were finally included in the study. CCTA images were reconstructed using iterative reconstruction, iterative reconstruction plus SSF1 and SSF2 algorithms. All images were divided into three groups: STD group, SSF1 group, and SSF2 group. The image quality of the CCTA images was assessed using the Likert scale, and differences between the two groups were compared using the Mann-Whitney U and Kruskal-Wallis test. The correlation and consistency between CT-FFR and FFR were evaluated using Spearman correlation coefficient and Bland-Altman plots. The diagnostic performance of CCTA and CT-FFR from three groups was compared by receiver operating characteristic (ROC) curves. The area under the curve (AUC) was compared using the DeLong test. Results:Compared to the STD group and SSF1 group, the SSF2 group showed the best performance in image quality score (median=3.7). Best correlation ( r=0.652, P<0.001) and consistency (mean difference=0.03) between CT-FFR and FFR were observed in SSF2 group. ROC analysis results revealed that, at the per-lesion level, in the diagnosis of ischemic lesions, the diagnostic performance of CT-FFR in the SSF2 group was significantly better than that of the SSF1 group (AUC=0.88 vs. 0.76, P=0.003), while no significant difference was observed between STD group and SSF1 group ( P=0.125). At the per-patient level, the SSF2 group also demonstrated the highest diagnostic performance. Conclusion:The SSF2 algorithm significantly improved CCTA image quality and enhanced its diagnostic performance for evaluating stenosis severity and CT-FFR calculations.

Sepsis is currently defined as a life-threatening multiple organ dysfunction caused by host dysregulated response to infection, with high morbidity and mortality in intensive care units. Patients with sepsis are often complicated with cardiac dysfunction known as septic cardiomyopathy (SCM). The occurrence of SCM is related to the high mortality of patients, which has been closely concerned for a long time, and is also one of the challenges to be solved in the systematic treatment of sepsis. A large number of studies have shown that oxidative stress contributes to the pathogenesis of SCM. The role of oxidative stress in SCM and the potential treatment measures for redox imbalance are discussed in this paper.

Objective:To evaluate the enrollment rate, mutation rate and causes of variability the clinical pathway of bronchopneumonia.Methods:The enrollment rate, completion rate, variation and reasons of the clinical pathway in Beijing Children′s Hospital, Capital Medical University from January 2012 to December 2016 were retrospectively collected.Data of patients after the clinical pathway of bronchopneumonia in other tertiary class A hospitals were gathered by questionnaires, and the enrollment rate, completion rate, variation rate and reasons were analyzed.Results:(1)At the end of 2016, 11 of the 13 hospitals included in this study had implemented the clinical pathway for 5 years, 1 hospital for 3 years, and 1 hospital for 2 years.(2) Eleven hospitals provided their enrollment rates.The enrollement rate of 2 hospitals was<50%, and that of 9 hospitals was>80%.The annual completion rate of Beijing Children′s Hospital was ≥75%, and the completion rates offered by 8 hospitals were basically >70%.(3) Since the implementation of the clinical pathway for 5 years in Beijing Children′s Hospital, a total of 427 cases were enrolled of which 93 cases were mutated (variability 21.78%). The variability of 5 hospitals was maintained at <15%.The variability of 3 hospitals decreased with the implementation years, and became qualified.The variability of 1 hospital first rebounded and then controlled; 1 hospital increased by 27.65%; 1 hospital was first controlled and rebounded; 1 hospital was always >15%.The main cause of the mutation was coexisting diseases, complications, progression of the disease, or correction of the first diagnosis, etc.Conclusions:The completion rate of tertiary class A hospitals meets the requirements of national policy.However, the enrollment rate needs to be improved, and the variation rate among different hospitals differs a lot.Further implementation of the clinical pathway should be strengthened and monitored.

Objective:To analyze the effect on the expressions of nuclear factor-erythroid 2-related factor 2(Nrf2) and NAD(P)H quinone oxidoreductase 1 enzyme (NQO1) in A549 cells exposed to hyperoxia and interfered by small interfering RNA, and to investigate the role of Nrf2 and NQO1 in hyperoxia-induced lung injury as well as their relationship with apoptosis.Methods:A549 cells were gained by serial sub cultivation in vitro and then randomly divided into 4 groups: the air group without interference ( group Ⅰ), the hyperoxia group without interference (group Ⅱ), the air group transfected with Nrf2 siRNA (group Ⅲ), and the hyperoxia group transfected with Nrf2 siRNA (group Ⅳ). The hyperoxia groups (Ⅱ, Ⅳ group) were continuously exposed to an atmosphere containing a high concentration of oxygen (950 mL/L O 2, 50 mL/L CO 2), while the air groups (group Ⅰ, Ⅲ) were still placed in the incubator with 50 mL/L CO 2. In the pre-experiment, cells were transduced with a mixture of siRNA-1, siRNA-2, and siRNA-3. Then the siRNA with the highest efficiency for repressing Nrf2 expression was used for subsequent experiments. The mRNA and protein expression levels of Nrf2 and NQO1 in the 4 groups were detected by quantitative real-time polymerase chain reaction (qPCR) and Western blot.The distribution of Nrf2, Kelch-like ECH-associated protein 1(Keap1) and antioxidant response element(ARE) proteins in A549 cells after interference with Nrf2 was analyzed by immunofluorescence and confocal laser scanning microscope, and the cell apoptosis of the 4 groups were observed. Results:(1) Nrf2 siRNA significantly down-regulated the mRNA expression of Nrf2 in the groups siRNA-1, siRNA-2 and siRNA-3, and the inhibition efficiency of group siRNA-1 was the highest (80.57%). (2) The re-lative mRNA expression levels of Nrf2 and NQO1 in the group Ⅱ were 4.553±0.498 and 5.866±0.582, respectively.The mRNA and protein expression of Nrf2 and NQO1 and the cell apoptosis rate [(21.67±0.75)%]in the hype-roxia group were significantly higher than those in the group Ⅰ (all P<0.01). (3) The relative mRNA expression levels of Nrf2 and NQO1 in the group Ⅳ were 0.937±0.057 and 0.789±0.058, respectively.Compared with the group Ⅱ, the mRNA and protein expression of Nrf2 and NQO1 in the group Ⅳ were significantly decreased, while the cell apoptosis rate [(35.83±0.42)%]was significantly increased (all P<0.01). Conclusions:The abnormal expression of Nrf2 and NQO1 in A549 cells induced by hyperoxia and siRNA interference suggests that Nrf2 and NQO1 are involved in the pathogenesis of hyperoxia induced lung injury.Nrf2 and NQO1 are possibly protective factors in the hyperoxia induced lung injury and apoptosis.

Animals ; Cdc20 Proteins/metabolism* ; Cell Line ; Embryo, Mammalian/embryology* ; Embryonic Development ; Female ; Infertility, Female/metabolism* ; Mice ; Mutation ; Oocytes/metabolism*

Objective To observe the antibacterial effects of amikacin sulfate combined with the ingredient of coptis chinensis:the extract of coptis chinensis, berberine hydrochloride and palmatine hydrochloride on multiple drug resistance (MDR) of Escherichia coli (E.coli) in vitro. Methods One hundred strains of E.coli checked out from 2013 to 2014 that showed resistence to cefotaxime were selected, and in which MDR to bacteria were determined. The extended-spectrum β-lactamases (ESBLs)-producing by Kirby-Bauer test. The minimum inhibitory concentrations (MIC) of the extract of coptis chinensis, berberine hydrochloride, palmatine hydrochloride and amikacin sulfate on ESBLs-producing E.coli were determined firstly, and then the sterilization effects of amikacin sulfate combined with the other three medicines were observed by broth microdilution checkerboard method together with their fractional inhibitory concentrations (FIC), with ATCC 25922 for quality control strains. Results Ten MDR E.coli were screened and proved to be ESBLs-producing. The inhibitory effects were enhanced in a synergistic or additive pattern when amikacin sulfate combined with the extract of coptis chinensis, berberine hydrochloride on nine of the ten MDR E.coli in vitro, where the inhibitory effects were a synergistic or additive pattern when amikacin sulfate combined with palmatine hydrochloride on all of the MDR E.coli in vitro. Conclusion Palmatine hydrochloride or berberine hydrochloride or the extract of coptis chinensis combined with the amikacin sulfate has significant value in treatment of MDR E.coli, which is worthy of further study.

Objective To explore MRI appearances of malignant mixed mesodermal tumors (MMMT) of the uterus. Methods All 9 patients with MMMT were proved by pathology. MRI characteristics of MMMTs in 9 patients were analyzed retrospectively.Results Of 9 MMMTs,6 were uterus body-based and 3 were cervical-based.Body-based MMMTs tended to be expansive or infiltrative growth with expanded uterus cavity. Cervical-based.MMMTs tended to be exophytic growth without myometrial infiltration. The tumors presented iso- or low signal on T1WI. The body-based MMMTs presented heterogeneously hyper-intense on T2WI ( n =5 ),hemorrhage ( n =1 ),cystic degeneration and necrosis (n =5) were seen within the tumors. Cervical-based MMMTs presented relative hyper-intense signal on T2WI with band or tree-like hypo-intense signal,without hemorrhage and necrosis. Body-based MMMTs were enhanced more obviously than cervical-based MMMTs.Conclusions The growth pattern,MRI signal and enhancement characteristics of cervix and uterus body MMMTs are different. MRI is helpful for the diagnosis of MMMT.