Objective To investigate the long-term incidence of in-stent stenosis(ISS)in patients with intracranial aneurysms receiving pipeline embolization device(PED)who showed no ISS at short-to-medium term follow-up examination.Methods The clinical data of patients,who received PED treatment at the Department of Neurointervention,First Affiliated Hospital of Zhengzhou University of China between April 2015 and June 2022,were retrospectively collected.The patients with intracranial aneurysms,who showed no ISS at the initial follow-up with DS A and completed＞12 months long-term follow-up check after treatment at the same hospital,were screened out,and their relevant clinical data and imaging materials were collected.The incidence of ISS occurring in postoperative＞12 months long-term follow-up was calculated.The ISS was defined as a＞25％lumen loss of the parent artery when compared with its lumen size measured immediately after PED implantation.Results A total of 57 patients with 61 aneurysms were enrolled in this study,and a total of 68 PEDs were implanted.Forty-one(67.21％)aneurysms were treated by PED implantation only,and 20(32.79％)aneurysms by PED plus spring coils.The median initial follow-up time was 184.0 days(119.0,212.5).At postoperative＞12 months long-term follow-up visit,DSA was employed for 35(57.38％)aneurysms,CTA was adopted for 22(36.07％)aneurysms,and 3D-SPACE sequence MR scan was performed in 4(6.56％)aneurysms.The median follow-up time was 538.0 days(407.5,678.0),and the incidence of ISS was 0％.No ISS-related neurological symptoms occurred in all patients.Conclusion In treating intracranial aneurysms with PED,the postoperative incidence of ISS is low.No ISS is found during the short-term follow-up period,and long-term follow-up results tend to indicate that no ISS events have occurred.

【Objective】 To analyze and mine the prescription rules of traditional Chinese medicine enema treatment of chronic kidney disease （CKD） in CNKI platform journals based on data mining and network pharmacology so as to find high-frequency core Chinese medicines and predict the potential targets of core Chinese medicines and explore the mechanism of action of core Chinese medicines in the treatment of CKD. 【Methods】 Taking CNKI as the data source， we retrieved the clinical literature of traditional Chinese medicine enema in the treatment of CKD. SPSS modeler 18.0 statistical software was used for statistical processing and association rule analysis. IBM SPSS statistics 21 statistical software was used for cluster analysis. BATMAN-TCM and TCMSP were used to retrieve the effective components and related targets of drugs. Genecards， OMIN， Drugbank， DisGenet， TTD， and PharmGkb databases were used to retrieve disease-related targets， and Venny platform was used to screen disease and drug intersection targets. We used STRING database to obtain relevant documents， Cytoscape 3.8.2 software for visual analysis， Metascape database for enrichment analysis， Wechat website to draw bubble diagram， and AutoDockTools-1.5.6 software for molecular docking prediction. 【Results】 We selected 276 effective prescriptions involving 120 traditional Chinese medicines. The frequency of 19 traditional Chinese medicines was more than 10. Totally 18 core drug combinations were obtained. Cluster analysis could be divided into four categories. The visual net-work analysis shows that “rhubarb， dandelion， oyster， Salvia miltiorrhiza and aconite” are highly correlated and occupy the core position. Through the prediction of the potential targets of five core drugs， 659 “drug disease” intersection targets and 173 core targets were obtained， of which “MAPK1， AKT1 and STAT3” are the key targets， “progesterone， neocryptotanshinone Ⅱ and emodin”. It is predicted that it may play a role in “PI3K Akt signal pathway， MAPK signal pathway， JAK-STAT signal pathway”. Molecular docking showed that the key components have good binding activity with key targets. 【Conclusion】 Based on data mining and network pharmacology， traditional Chinese medicine enema treatment of CKD mainly uses rhubarb as the main drug， assisting warming yang to remove blood stasis and turbidity relief drugs. The key components of its core drug can act on PI3K-Akt by regulating key targets such as PIK3R1. Signal pathways and other pathways play a role in providing new ideas for the treatment of this disease with traditional Chinese medicine enema， medication strategies for clinical prescriptions， and a basis for follow-up further research.

Objective::Long-term diabetes can result in ventricular hypertrophic remodeling, tissue fibrosis, myocardial metabolic defection, and eventually, heart failure. Silent information regulator 6 (SIRT6) exerts beneficial effects against cardiovascular diseases. This study is aimed to investigate whether the direct regulation of myocardial SIRT6 signaling affects cardiac performance in the case of diabetes. Meanwhile, we sought to explore the underlying mechanisms.Methods::Sprague Dawley (SD) rats were used in this experiment. Briefly, type 2 diabetic animal model was generated by streptozotocin administration along with feeding a high-fat diet. The SD rats were randomly assigned to non-diabetic group, diabetic group, diabetic injected with empty adenoviral vectors group and diabetic injected with adenoviral vectors expressing SIRT6 group ( n = 10, respectively). The animals were kept for another 4 weeks before sacrifice. Cardiac performance was evaluated by echocardiography. Myocardial fibrosis was determined by Masson’s trichrome staining. Myocardial SIRT6 signaling and fibrosis related molecules were measured by western blotting. Results::The diabetic myocardium exhibited markedly enhanced TGFβ1-Smad2/3-induced myocardial fibrosis and reduced SIRT6 and AMP-activated protein kinase (AMPK) signaling. After 4 weeks of SIRT6 adenoviral vector infection, myocardial tissues exhibited markedly enhanced SIRT6 and AMPK signaling. Additionally, myocardial fibrosis and TGFβ1 -Smad2/3 signaling were both attenuated in the diabetic injected with adenoviral vectors expressing SIRT6 group.Conclusions::SIRT6-AMPK signaling suppressed the progression of tissue fibrosis in diabetes mellitus rats by inhibiting TGFβ1 and its downstream effector Smad2/3. SIRT6 might serve as an alternative therapeutic target for diabetes-related cardiovascular diseases.

Objective::Long-term diabetes can result in ventricular hypertrophic remodeling, tissue fibrosis, myocardial metabolic defection, and eventually, heart failure. Silent information regulator 6 (SIRT6) exerts beneficial effects against cardiovascular diseases. This study is aimed to investigate whether the direct regulation of myocardial SIRT6 signaling affects cardiac performance in the case of diabetes. Meanwhile, we sought to explore the underlying mechanisms.Methods::Sprague Dawley (SD) rats were used in this experiment. Briefly, type 2 diabetic animal model was generated by streptozotocin administration along with feeding a high-fat diet. The SD rats were randomly assigned to non-diabetic group, diabetic group, diabetic injected with empty adenoviral vectors group and diabetic injected with adenoviral vectors expressing SIRT6 group ( n = 10, respectively). The animals were kept for another 4 weeks before sacrifice. Cardiac performance was evaluated by echocardiography. Myocardial fibrosis was determined by Masson’s trichrome staining. Myocardial SIRT6 signaling and fibrosis related molecules were measured by western blotting. Results::The diabetic myocardium exhibited markedly enhanced TGFβ1-Smad2/3-induced myocardial fibrosis and reduced SIRT6 and AMP-activated protein kinase (AMPK) signaling. After 4 weeks of SIRT6 adenoviral vector infection, myocardial tissues exhibited markedly enhanced SIRT6 and AMPK signaling. Additionally, myocardial fibrosis and TGFβ1 -Smad2/3 signaling were both attenuated in the diabetic injected with adenoviral vectors expressing SIRT6 group.Conclusions::SIRT6-AMPK signaling suppressed the progression of tissue fibrosis in diabetes mellitus rats by inhibiting TGFβ1 and its downstream effector Smad2/3. SIRT6 might serve as an alternative therapeutic target for diabetes-related cardiovascular diseases.

Objective:To evaluate the efficacy and prognosis of endoscopic submucosal dissection (ESD) for undifferentiated-type early gastric cancer (EGC).Methods:Data of 393 patients with 400 EGC lesions who underwent ESD between January 2010 and April 2019 in the First Affiliated Hospital of Nanjing Medical University were collected in the retrospective study. Patients were divided into undifferentiated-type group (50 cases with 50 lesions) and differentiated-type group (343 cases with 350 lesions) according to postoperative pathology. Their data including age, gender, size and location of the resected lesion, general classification, depth of infiltration, presence or absence of ulcers, and follow-up were compared.Results:Logistic regression analysis showed that age ≤60 years ( OR=2.02, 95% CI: 1.04-3.95, P=0.011), female ( OR=2.83, 95% CI: 1.41-5.68, P=0.003), gastric antrum lesions ( OR=3.92, 95% CI: 1.65-9.30, P=0.002), endoscopic depressed type ( OR=5.37, 95% CI: 2.16-13.38, P<0.001), and submucosa invasive depth ( OR=5.09, 95% CI: 2.40-10.80, P<0.001) were independent risk factors for undifferentiated EGC. The undifferentiated-type group showed a significantly higher non-curative resection rate [90.0% (45/50) VS 19.8% (68/343), χ2=104.902, P<0.001]. Of the 393 patients, 5(4.4%) died in the 113 patients with non-curative resection, while 2 (0.7%) died in the 280 patients with curative resection. Patients with non-curative resection had a higher mortality ( χ2=5.558, P=0.023). There were 27 and 51 patients undergoing additional surgery in the undifferentiated-type group and the differentiated-type group, respectively. None of them had recurrence. Among the 315 patients who did not undergo surgery, the recurrence rate of the undifferentiated-type group was significantly higher than that of the differentiated-type group [26.1% (6/23) VS 4.1% (12/292), χ2=5.560, P<0.001]. Conclusion:Young age (≤60 years), female, gastric antrum lesions, endoscopic depressed type, and submucosa invasive depth are predictors of undifferentiated EGC. Patients with undifferentiated EGC have a higher non-curative resection rate and higher possibility of recurrence after ESD, and additional operation are suggested.

Objective? To investigate the changes of body temperature and the effect of nursing intervention in patients with low body mass index (BMI＜18.5 kg/m2) during thoracic surgery. Methods? Sixty patients with low BMI who underwent thoracic surgery in the Operating Department of the 4th Hospital of Hebei Medical University from June 2016 to December 2018 were randomly divided into observation group and control group, with 30 cases in each group. In addition, 30 patients with normal BMI (18.5-23.0 kg/m2) who underwent thoracic surgery in the same period were selected as the normal group. The observation group adopted comprehensive thermal insulation measures during the operation, and the control group and the normal group adopted routine insulation measures. The patient's body temperature of three groups was compared at each time point: entering operation room, disinfection, body cavity exploration , cutting specimens, closing the chest, suture skin and exiting operation time. the occurrence of adverse reactions during surgery, the blood coagulation index and lactic acid in the peripheral blood before and at the end of surgery, and the peripheral blood inflammatory factor levels were also compared. Results? There were no significant differences in body temperature between the three groups (P＞ 0.05). During the operation, the body temperature of the three groups decreased, and the recovery from the chest was restored. There were significant differences in body temperature between the three groups (P＜ 0.05) at the time point: closing the chest, suture skin and exiting operation room. The incidence of adverse reactions in the observation group was lower than that in the control group and the normal group, and the difference was statistically significant (P＜ 0.05). There was no significant difference in the incidence of adverse reactions between the control group and the normal group (P＞ 0.05). The coagulation and stress indexes of the observation group and the control group were significantly different from those of the normal group (P＜ 0.05). There was no significant difference in the coagulation,lactic acid and stress indexes between the observation group and the control group (P＞ 0.05). The coagulation, lactic acid and stress indexes of the three groups were significantly different before and after surgery (P＜ 0.05). There was a statistically significant difference in interleukin-6(IL-6) levels before and after surgery (F=134.241, P＜ 0.001); there was an interaction between the intervention and the time, and the difference was statistically significant (Finteraction =12.202, P＜0.001). There were significant differences between the three groups in the interleukin-10(IL-10) level group (between group F=7.792, P ＜ 0.001); the difference of IL-10 levels before and after surgery was statistically significant (Ftime=112.121, P＜ 0.001); There was an interaction between the intervention and the time, and the difference was not statistically significant (Finteraction=2.990,P=0.055). Conclusions? Compared with patients with normal BMI thoracic surgery, patients with low BMI have abnormal blood coagulation and stress indicators before surgery, and are more likely to have intraoperative blood pressure drop and adverse reactions. Comprehensive intraoperative warming measures can effectively prevent hypothermia in patients with low BMI.

Objective To study the utility of fibrin glue on prevention of bleeding after endoscopic submucosal dissection ( ESD).Methods Consecutive patients with gastrointestinal tumors who underwent ESD between July 2015 and June 2016 in the First Affiliated Hospital of Nanjing Medical University were enrolled in the study. The patients receiving ESD before December 31, 2015 were assigned into the fibrin glue group, and patients receiving ESD after December 31, 2015 were assigned into the control group. The fibrin glue group was sprayed with fibrin glue on wound followed by routine hemostasis method, and the control group was given routine hemostasis method only. The bleeding rate after ESD, mean hospital stays and cost were compared between the two groups.Results The bleeding rate after ESD in the fibrin glue group was significantly lower than that in the control group[7. 45%(12/161) VS 14. 79%(25/169), P＝0. 035]. There was no significantly difference in the mean hospital stays (9. 09±2. 65 days VS 9. 20±2. 99 days, P＝0. 744) and mean cost (24 246±5 519 yuan VS 25 214±6 258 yuan, P＝0. 138) between the two groups.Multivariate analysis revealed that the use of fibrin glue was a protective factor for bleeding after ESD. Conclusion Fibrin glue is safe, effective and economical in prevention of bleeding after ESD.

Objective: To explore the effects of endoplasmic reticulum stress-induced apoptosis in thyroid injury of rats caused by excessive fluoride intake. Methods: All 40 Wistar rats were randomly divided into four groups, control group, low fluoride group, medium fluoride group and high fluoride group. The rats in control group were fed with tap water (fluoride concentration=0.344 mg/L) and the experimental rats were fed with the water contaminated fluoride with the dose of 5, 10 and 20 mg/L. 10 rats (female: male=1∶1) in each group were sacrificed after 8 months of exposure through drinking water. The contents of urine fluoride were detected by fluorine ion selective electrode method. Morphology of thyroid was observed through light microscope and apoptosis in thyroid were detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The mRNA and protein expressions of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) were analyzed by RT-PCR and immunohistochemistry respectively, and results were compared among groups. Results: The contents of urine fluoride in all fluoride treated groups were separately (4.74±1.88), (7.70±2.82) and (10.50±2.92) mg/L, which were gradually higher than that of control group (2.23±0.54) mg/L (P<0.05). Morphological changes were found in thyroid tissues of fluoride treated groups, thyroid follicular hyperplasia or even no cavity cell clusters were observed. Apoptosis in thyroid were notably increased in fluoride treated groups. The mRNA expression levels of GRP78 in all fluoride treated groups were separately 1.30±0.42, 1.39±0.29 and 1.50±0.27, which were significantly higher than that of control group (0.93±0.24) (P<0.05). And the mRNA expression levels of CHOP in medium and high fluoride groups were separately 1.17±0.29 and 1.30±0.26, which were significantly higher than that of control group (0.91±0.20) (P<0.05). The protein expression levels of GRP78 and CHOP in medium and high fluoride groups were respectively 29.68±4.04, 29.90±3.74 and 4.05±1.62, 4.44±1.81, which were significantly higher than those in the control group (separately 23.80±6.36, 2.27±0.89) (P<0.05). Conclusion Excessive-fluoride intake can induce thyroid injury, and endoplasmic reticulum stress-induced apoptosis might be involved in the injury.

Breast cancer is the principal cause of death in malig-nancy women , usually treated with the combination of surgery , chemotherapy , radiotherapy and endocrinotherapy .With the de-velopment of cell biology , molecular biology , immunology, im-munotherapy becomes a new field of breast cancer treatment .In this review, we discuss new findings in breast cancer immuno-therapy , including recent successes with bispecific antibodies and immune checkpoint blockade .We also discuss therapeutic cancer vaccines and highlight several additional immunotherapy modalities in early stages of development .

OBJECTIVE:To investigate the effects of Astragalus injection combined with Salmeterol propionate powder inhala-tion on pulmonary function,cytokines and blood rheology indexes of Chronic obsrnctine pulmonary disease (COPD) patients. METHODS:104 COPD patients were divided into observation group and control group according to the randorn number table meth-od,with 52 cases in each group. Control group was given routine symptomatic treatment+Salmeterol propionate powder inhalation 1 dose,bid;observation group was additionally given Astragalus injection 30 ml added into 5% Glucose injection 250 ml,ivgtt, qd,on the basis of control group. Treatment course of 2 groups lasted for 2 weeks. Clinical efficacy,pulmonary function indexes [forced expiratory volume in one second(FEV1),forced vital capacity(FVC),FEV1/FVC],CRP,cytokine [IL-6,IL-8,TNF-α] levels,blood rheology indexes (whole blood high-shear viscosity,whole blood low-shear viscosity,fibrinogen,hematokrit and plasma viscosity),and the occurrence of ADR were observed in 2 groups. RESULTS:The total effective rate of observation group (94.23%)was significantly higher than that of control group(75.00%);compared with before treatment,FEV1,FVC and FEV1/FVC of 2 groups were significantly increased after treatment,and those of observation group were significantly higher than those of control group;CRP,IL-6,IL-8 and TNF-α of 2 groups were significantly decreased,and those of observation group were signifi-cantly lower than those of control group. The whole blood high-shear viscosity,whole blood low-shear viscosity,fibrinogen,hema-tocrit and plasma viscosity of observation group were decreased significantly after treatment,and the observation group was signifi-cantly lower than the control group,with statistical significance(P<0.05). No significant ADR was found in 2 groups. CONCLU-SIONS:Astragalus injection combined with Salmeterol propionate powder inhalation is significantly effective for COPD,improves pulmonary function of patients,improves micro inflammatory state and decreases blood rheology indexes with good safety.