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 evaluate the correlation between ultrasound parameters of internal carotid artery blood flow and regional cerebral oxygen saturation (rScO 2) in elderly patients undergoing coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB). Methods:Sixty-four elderly patients undergoing elective CABG under CPB, aged 60-80 yr, regardless of gender, with body mass index of 18.1-28.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with New York Heart Association class Ⅱ or Ⅲ, with left ventricular ejection fraction≥50%, were selected. The rScO 2 and ultrasonic parameters of internal carotid artery including peak systolic velocity (PSV-ICA), end-diastolic velocity (EDV-ICA), diameter (D-ICA) and blood flow volume (Q-ICA) were recorded before anesthesia induction (T 0), at surgical skin incision (T 1), at 30 and 60 min of CPB (mean value was calculated, T 2), and at 30 and 60 min after termination of CPB (mean value was calculated, T 3). The ratio of unilateral internal carotid artery blood flow to cardiac output (Q/CO) was calculated. The receiver operating characteristic curve was used to analyze the accuracy of ultrasound parameters of internal carotid artery blood flow in predicting rScO 2 < 60%. Results:PSV-ICA was positively correlated with rScO 2 at T 0, T 1 and T 3 ( P<0.05), but no correlation was found between PSV-ICA and rScO 2 at T 2 ( P>0.05). There was no correlation between EDV-ICA and rScO 2 at each time point ( P>0.05). Q-ICA was positively correlated with rScO 2 at each time point ( P<0.05). Q/CO was not correlated with rScO 2 at T 1 ( P>0.05), but Q/CO was positively correlated with rScO 2 at T 2 and T 3 ( P<0.05). During the non-CPB period (T 0, T 1, T 3), the cutoff values of PSV-ICA and Q-ICA in predicting rScO 2< 60% were 51.35 cm/s and 283.5 ml/min respectively, the sensitivity was 0.900 and 0.900 respectively, and the specificity was 0.610 and 0.857 respectively (AUC=0.761, P=0.006; AUC=0.903, P< 0.001). During the CPB period, the cutoff values of Q-ICA and Q/CO in predicting rScO 2<60% were 296.5 ml/min and 5.84% respectively, the sensitivity was 0.900 and 0.800, and the specificity was 0.545 and 0.659 (AUC=0.764, P=0.001; AUC=0.748, P=0.002), respectively. Conclusions:PSV-ICA and Q-ICA are positively correlated with rScO 2 during the non-CPB period, and Q-ICA and Q/CO are positively correlated with rScO 2 during the CPB period in elderly patients undergoing CABG. PSV-ICA, Q-ICA and Q/CO can accurately predict rScO 2<60%.

Objective:To discuss the differences in eosinophil(EOS)infiltration in cervical tissue and its relationship with cervical-related diseases,and to clarify the effect of EOS on the occurrence and development of cervical intraepithelial neoplasia(CIN)and cervical cancer.Methods:The clinical data of 256 patients with cervical diseases were collected and divided into cervical cancer group(n=46,including 26 cases of squamous cell carcinoma,15 cases of adenocarcinoma,and 5 cases of adenosquamous carcinoma),chronic cervicitis group(n=50),CIN stage Ⅰ group(n=50),CIN stage Ⅱ group(n=50),CIN stage Ⅲ group(n=30),and normal group(adjacent normal cervical tissue,n=30)based on their conditions.Colposcopy was used to observe the morphology of cervical tissue of the patients in various groups;thin-layer liquid-based cytology test(TCT)was used to observe the morphology of the cervical exfoliated cells in various groups;hybrid capture-chemiluminescence method was used to detect the human papillomavirus(HPV)infection in cervical tissue of the patients in various groups;HE staining was used to observe the pathomorphology of cervical tissue of the patients in various groups;Congo red staining was used to detect the numbers of EOS infiltration in cervical tissue of the patients in various groups;Pearson correlation analysis was used to analyze the correlation between the number of EOS infiltration and the malignancy degree of cervical cancer.Results:The cervical surface of the patients in normal group was smooth and pink,with uniformly distributed capillaries;the cervical surface of the patients in chronic cervicitis group showed red inflammatory changes,with some accompanied by Nabothian cysts and varying degrees of erosion and ulcers;the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups showed epithelial ulcers,thickening,and irregular morphology,with mosaic and punctate vessels;the cervical surface of the patients in cervical cancer group showed raised areas with neoplasms and necrotic ulcers,and they were fragile and prone to bleeding.After acetic acid staining,no obvious changes of the patients in normal group were observed.The cervix of the patients in chronic cervicitis group showed slight white changes that lasted for a short time;in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,irregular thin acetowhite epithelium with map-like borders was observed,with increasingly acetowhite reactions and larger areas as the stages advanced.The cervix of the patients in cervical cancer group showed thick acetowhite epithelium that lasted longer,with rigid and clear contours.After iodine staining,the cervix of the patients in normal group was brown,with uniform coloration;the cervix of the patients in chronic cervicitis group showed poor coloration in inflammatory lesion areas;the cervix of the patients in CIN stage Ⅰ group showed iodine coloration in metaplastic areas,while the cervix of the patients in CIN stage Ⅲ group showed poor coloration in larger lesion areas;the cervix of the patients in cervical cancer group showed irregular surfaces with cauliflower-like growth and no coloration after iodine staining,appearing orange-yellow or mustard yellow.The TCT observation results showed there were no heteromorphic cells and few inflammatory cells in cervical exfoliated cells of the patients in infiltration in normal group;there were numerous neutrophils and EOS in exfoliated cervical cells without heteromorphic cells in chronic cervicitis group.The heteromorphic binucleated cells with high nuclear-cytoplasmic ratios and deeply stained nuclei were observed in cervical exfoliated cells of the patients in CIN stage Ⅰ and CIN stage Ⅱ groups.More heteromorphic cells with high nuclear-cytoplasmic ratios and irregular nuclear membranes were showed in cervical exfoliated cells of the patients in CIN stage Ⅲ group.The cervical exfoliated cells of the patients in cervical cancer group showed large and prominent nucleoli,clustering into syncytial changes.Compared with normal group,the atypial of cervical exfoliated cells in CIN stage Ⅰ,CIN stage Ⅱ,CIN stage Ⅲ,and cervical cancer groups was increased.The hybrid capture-chemiluminescence results showed that compared with normal and chronic cervicitis groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in cervical cancer group were increased(P<0.05).The HE staining results showed normal cell morphology and structure in normal group,with infiltration of inflammation cells such as neutrophils,monocytes,macrophages,EOS,and lymphocytes;in chronic cervicitis group,the infiltration of inflammatory cells was increased;in CIN group,the cervical cells showed slightly larger nucleoli and heteromorphic cells,with inflammatory cells mainly distributing around the hetermomorphic cells;in cervical cancer group,the cervical cells showed large and deeply stained nucleoli with significant atypia,and the infiltration of inflammatory cells around the cancer cells was increased.Compared with normal group,the numbers of inflammatory cells and EOS infiltration in cervical tissue of the patients in chronic cervicitis group were increased(P<0.05),and the numbers of inflammatory cells and EOS infiltration of the patients in CIN group were increased(P<0.05);compared with chronic cervicitis group,the number of inflammatory cells and EOS infiltration of the patients in CIN group were decreased(P<0.05);compared with chronic cervicitis group and CIN group,the numbers of inflammatory cells and EOS infiltration of the patients in cervical cancer group were increased(P<0.05).The EOS in cervical cancer tissue was mainly distributed around the cancer nests;compared with CIN stage Ⅰ group,the numbers of EOS infiltration in CIN stage Ⅱ and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅱ group,the number of EOS infiltration in CIN stage Ⅲ group was increased(P<0.05).The higher the malignancy degree of the tumor,the more EOS infiltration was observed,and the number of EOS infiltration was positively correlated with the invasion depth of cervical cancer(r=0.533 0,P<0.01).Conclusion:HPV infection and EOS infiltration play a role in promoting the and occurrence development of cervical precancerous lesions and cervical cancer.

Objective To assess the impact of intravenous esketamine administered prior to car-diopulmonary bypass(CPB)initiation on ventricular function and internal carotid artery blood flow in pa-tients undergoing heart valve replacement surgery.Methods Sixty patients underwent elective CPB heart valve replacement,38 males and 22 females,aged 18-75 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅱ or Ⅲ,NYHA cardiac function classification Ⅰ-Ⅲ,and a left ventricular ejection fraction(LVEF)of≥45％,were selected.The patients were randomly divided into two groups:esketamine group(group E)and normal saline group(group C),30 patients in each group.Total intravenous anesthesia was used during the operation.Following the initiation of CPB,group E received an intravenous infusion of es-ketamine at a rate of 0.5 mg·kg-1·h-1 until the conclusion of the procedure,while group C received an equivalent volume of normal saline concurrently at the same rate.HR,MAP,CVP,and cardiac output index(CI)were recorded before anesthesia induction,during skin resection,and within 60 minutes after stopping CPB.LVEF,left ventricular global longitudinal strain(GLS),global longitudinal time-to-peak strain standard deviation(GLTSD),global circumferential strain(GCS),global circumferential time-to-peak strain standard deviation(GCTSD),right ventricular ejection fraction(RVEF),right ventricular GLS,and GLTSD were obtained during skin resection,within 40 minutes of CPB,and 60 minutes after stopping CPB.rScO2,BIS,concentrations of Hb and lactic acid(Lac),peak systolic flow velocity(SPV),quantity of flow-internal carotid artery(Q-ICA),and blood flow resistance index(RI)were recorded before anesthesia induction,during skin resection,within 40 minutes of CPB,and within 60 minutes after stopping CPB.Concentrations of cardiac troponin Ⅰ(cTnⅠ),alanine aminotransferase(ALT),creatinine(Cr),and neuron-specific enolase(NSE)were recorded before anesthesia induction and 6 hours after operation.Spon-taneous resuscitation after CPB,postoperative extubation time,duration of ICU stay,total hospital stay,in-cidence of adverse cardiac events,and 30-day postoperative mortality were recorded.Results Compared with group C,group E exhibited a significant increase in CI within 60 minutes after stopping CPB(P＜0.05).The LVEF,RVEF,and right ventricular GLS demonstrated significant increases within 60 minutes after stopping CPB in group E compared with group C(P＜0.05).The left ventricular GLS and left ven-tricular GCTSD displayed significant increases 30 minutes after stopping CPB in group E compared with group C.The RI exhibited a significant increase within 40 minutes of CPB in group E compared with group C(P＜0.05).There were no significant differences in cTnⅠ,ALT,Cr,NSE,spontaneous resuscitation affter CPB,postoperative extubation time,duration of ICU stay,total hospital stay,incidence of cardiac adverse events,and 30-day postoperative mortality between the two groups.Conclusion Administration of esket-amine following the onset of CPB in patients undergoing cardiac surgery demonstrates a significant elevation in CI post-CPB cessation.Furthermore,it may augment ventricular longitudinal strain,thereby enhancing myocardial contraction,leading to increased postoperative ventricular ejection fraction,and sustaining hemo-dynamic stability.

Dengue viruses(DENV) are seriously affected by cell autophagy in intracellular replication,transmission between host,and the pathogenic mechanism.Here,the latest research progress of complex interplay between DENV and cell autophagy were reviewed in this paper.Autophagy,a cellular procedural protein degradation pathway generally possessed by all eukaryotes plays a key role in response to outside pressure and maintaining cellular homeostasis.This catabolic pathway also promotes cell survival against the invasion of pathogens such as various viruses.However,autophagy plays an opposite role in the replication of DENV.Autophagy not only provides a replication site for viruses to replicate,but also provides a source of energy for this process.Cell autophagy also participates in the pathogenesis of some DENV infection.In short,autophagy contributes to the replication of DENV.

Objective: To explore the spatial-temporal distribution and epidemic characteristics of hemorrhagic fever with renal syndrome (HFRS) in Hebei province from 2005 to 2016. Methods: Records of HFRS cases reported from each county in Hebei during January 2005 to December 2016 were collected from National Notifiable Disease Surveillance System (NNDSS). Global and local spatial association statistics were used to measure the spatial autocorrelation and software GeoDa 1.2.0. Software SaTScan 9.4.1 was used to analyze spatiotemporal clusters. Software ArcGIS 10.2 was used to visualize the yearly scan results. Results: In Hebei province, a total of 8 437 human HFRS cases reported from 170 counties with an annual incidence rate of 0.99/100 000 population during 2005-2016. The peak incidence season was spring. Global spatial autocorrelation analysis on the incidence of HFRS at county-level showed that the value of Moran’s I were all above 0 (P<0.05), indicating that the significant spatial cluster. The result of local indicators on spatial association (LISA) analysis revealed that identified hot spots were mainly in northeastern area, while cold spots were found in some counties of central and southern areas. Spatial-temporal scan detected that the primary cluster of HFRS incidence was mainly distributed in Qinhuangdao city and Tangshan city, including 11 counties (city/district): Beidaihe district, Haigang district, Funing district, Shanhaiguan district, Changli county, Lulong county and Qinglong Manchu autonomous county in Qinhuangdao city, and Qian’an city, Laoting county, Luanzhou city and Luannan county in Tangshan city (RR=39.64, P<0.001), during January-July in 2005. Conclusions There were significant spatial-temporal cluster of HFRS in Hebei from 2005 to 2016. The cluster areas of HFRS were mainly in northeastern Hebei, it is necessary to strengthen the prevention and control programs of HFRS in these areas.

Objective: To analyze the research hotspots of domestic narrative nursing and explore its related research trends which provide reference and guidance for its application and development in China. Methods: Wanfang, CNKI, VIP, CBM and other databases were retrieved from inception until October 2018. Word frequency analysis and graph cluster analysis were performed on the main information using Excel, Bicomb, Ucinet, Netdraw and gCLUTO software. Results: A total of 649 articles were included. The result of visual analysis showed that the annual amount of publications showed an upward trend. The articles distributed abroad in many different journals which educational journals account mostly. The study regions were distributed in 34 provinces except Taiwan of China, Hainan, Tibet, and Macao Special Administrative Regions where mainly concentrated on East China and North China. The cooperation among authors and institutions both were not close; A total of 25 high-frequency key words were intercepted,and three hotspots of narrative nursing research in China were obtained,which respectively were: (1) The application of narrative medicine and the cultivation of narrative ability; (2) The application research of narrative therapy in humanistic care; (3) The application of narrative nursing in nursing practice. Conclusions Narrative nursing has attracted the attention of domestic scholars, but the depth and breadth of research still need to be improved. It is necessary to strengthen cooperation between inter-regional institutions, individuals and scientific research groups and pay attention to research hotspots in this field. Also,there is a need to conduct more high quality studies to verify the significance of narrative nursing.

Objective Using meta-analysis to assess the association between maternal 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and the risk of offspring congenital heart defect (CHD) in Chinese population.Method PubMed,Embase,Web of science,Chinese Biomedical Literature Database,Chinese Science and Technology Academic Journal,Chinese Journal Full-text Database and Wanfang database were searched extensively from since their inception to January 2017 for relevant case-control studies.Odds ratio (OR) of MTHFR C677T genotype distributions in patients with CHD and healthy controls was calculated.Pooled OR calculation was analyzed by revMan 5.3software.Result A meta-analysis of nine case-control studies included 1 221 cases and 1 108 controls.There was association between maternal MTHFR gene C677T and the CHD of offspring and the pooled OR (95 ％ CI) of maternal TT/TC,TT/CC,TC/CC,TT/TC + CC and TT + TC/CC were 1.85 (95 ％ CI 1.50 ～2.28),2.33 (95％CI 1.81 ～3.00),1.24 (95％CI 1.00 ～ 1.54),2.00 (95％ CI 1.64 ～2.44) and 1.55 (95 ％ CI 1.27 ～ 1.89) (P ＜ 0.05),respectively.Conclusion There was association between maternal MTHFR C677T polymorphism and risk of offspring CHD in the Chinese population.

Objective To evaluate the effect of individualized food composition table on serum phosphorus management for patients undergoing peritoneal dialysis(PD). Methods A total of 83 patients who were treated with PD for over 3 months with serum phosphorus greater than 1.78 mmol/L were included from March to May 2016 in PD Center of the Second Hospital of Hebei Medical University by convenient sampling. They received dietary guidance with individualized food composition table and stable phosphorus binding agent. After 6 months, level of serum phosphorus, biochemical indicators and other PD indicators before and after the intervention were compared. Results After 6 months of diet intervention, the patients' serum phosphorus achieved rate was 71%. Serum phosphorus, potassium, parathyroid hormone decreased, and hemoglobin, serum albumin increased (P<0.05). For the PD indicators, blood pressure control was improved (P<0.05), and the rest of the indicators had no difference compared with those before intervention (P>0.05). Conclusions Dietary intervention based on individual food composition table can effectively reduce the serum phosphorus levels in patients with PD,and improve the nutritional status and simplify education working process of the PD center diet as well.

OBJECTIVE:To evaluate the effects and safety of Bencycloquidium bromide nasal spray in the treatment of acute rhinitis after a cold. METHODS:A multicenter,dose parallel controlled,randomized,double-blind,placebo-controlled clinical tri-al was conducted. Two hundred and thirty-eight patients with acute rhinitis after a cold were selected and divided into group A(24 cases),B(24 cases),C(24 cases),D(24 cases),E(23 cases),F(24 cases),G(23 cases),H(24 cases),I(24 cases),J (24 cases). Group A-C were given Bencycloquidium bromide nasal spray 22.5μg,45μg,90μg,respectively,bid,spraying it once for each nostril. Group D-F were given Bencycloquidium bromide nasal spray 22.5 μg,45 μg,90 μg,respectively,tid,spraying it once for each nostril. Group G-I were given Bencycloquidium bromide nasal spray 22.5 μg,45 μg,90 μg,respectively,qid,spray-ing it once for each nostril. Group J was given placebo. All groups were treated for(4±1)d. Rhinorrhea score and continuous rhi-norrhea duration were compared among 10 groups,and the safety was evaluated. RESULTS:The rhinorrhea score and continuous rhinorrhea duration of 10 groups were improved significantly,with statistical significance (P<0.05). The improvement and trend of group I was slightly better than other 9 groups,without statistical significance(P>0.05). There was no statistical significance in the incidence of ADR among 10 groups(P>0.05). CONCLUSIONS:Bencycloquidium bromide nasal spray with 90 μg,qid times significantly improves rhinorrhea score and continuous rhinorrhea duration with good safety.