Objective To observe the incidence of pericardial tamponade(PT)after left atrial appendage closure(LAAC)in patients with non-valvular atrial fibrillation(NVAF),and to explore its related factors and outcomes.Methods NVAF patients who were hospitalized and treated with LAAC in Department of Cardiology of our hospital from August 2014 to March 2023 were selected for the study.The general clinical data,preoperative transthoracic echocardiography and transesophageal echocardiography data,results of routine preoperative laboratory tests,intraoperative data and follow-up data of the patients were collected through the hospital medical record management system.The enrolled patients were classified into the non-PT group(n=8)and the PT group(n =1184)according to whether PT occurred after LAAC or not.The incidence of PT,related risk factors and outcomes were statistically analyzed.Results This study included 639 males(53.6%)and 553 females(46.4%),with an average age of 68.1±9.65 years.The CHA2 DS2-VASc score was 4.51±1.72,and the HAS-BLED score was 3.36±1.09.PT occurred in 8 cases(0.67%),among them,6 cases occurred 1 to 33 h after LAAC,and 2 cases occurred on day 19 and day 27 after LAAC.As for the results of transesophageal echocardiography(TEE)and LAA angiography,compared with the non-PT group,the PT group had the significantly larger maximum caliber of the LAA(P=0.025,P=0.015),smaller maximum depth of the LAA(P=0.028,P=0.031),and lower success rate of one-time placement of the occluder(P=0.031);The occluder compression rate of the PT group was significantly greater than that of the non-PT group(P=0.046).Multivariate analysis showed that larger maximum diameter of LAA,smaller average effective depth of LAA and larger compression rate of occluder were the main risk factors for PT.All the 8 PT patients were cured by stopping antithrombotic drugs,pericardiocentesis or surgical drainage.During a mean follow-up of 39±27 months,there were no device-related thrombosis(DRT),ischemic stroke,systemic embolism and other complications in the PT group.Conclusion The incidence of PT after LAAC is low,which is related to the large diameter of LAA,the relatively insufficient depth of the LAA and the large compression rate of the occlude.PT can be cured by stopping antithrombotic drugs and pericardiocentesis/surgical drainage.

Objective To observe the value of MR lymphangiography(MRL)radiomics for evaluating central conducting lymphatic anomaly(CCLA).Methods Sixty-one patients with complex lymphatic anomaly,including 41 CCLA(group A),20 non-CCLA(generalized lymphatic anomaly and Gorham-Stout disease)and 20 subjects with normal thoracic duct(group B,n=38)were retrospectively enrolled.Cervical and thoracic(combined with abdominal if necessary)MRL was acquired using three-dimensional heavily T2W fast spin echo sequence.ROI was delineated along overall thoracic duct,and radiomics features were extracted.Data sets of group A and B were divided into K subsets using 5-fold cross-validation.The union of(K-1)subset was always used as training set,while the other subsets were used as validation set.Radiomics model was constructed based on support vector machine(SVM)algorithm.Receiver operating characteristic curve was drawn,the area under the curve(AUC)was calculated to evaluate the efficacy of SVM model for assessing CCLA.Results The proportions of bifurcation,cystoid change and extension of main thoracic duct,and extension of terminal thoracic duct in group A were all higher,while of normal main and terminal thoracic duct in group A were both lower than those in group B(all P＜0.05).No significant difference of proportions of multiple thoracic ducts,dextral thoracic duct,part of thoracic duct invisible,multiple terminal thoracic ducts,cystoid change of terminal thoracic duct nor terminal thoracic duct pampiniform was found between groups(all P＞0.05).The sensitivity,specificity,accuracy,positive predictive,negative predictive and AUC of SVM model for evaluating CCLA in training set was 78.95％,97.56％,88.61％,96.77％,83.33％and 0.920,respectively,which in validation set was 78.95％,83.57％,82.28％,83.33％,81.40％and 0.833,respectively.Conclusion MRL radiomics could be used to effectively evaluate CCLA.

Rats ; Animals ; Urinary Bladder Neck Obstruction/pathology* ; Survivin/genetics* ; Urinary Bladder/pathology* ; Fibrosis

Bacterial antitumor therapy has great application potential given its unique characteristics, including genetic manipulation, tumor targeting specificity and immune system modulation. However, the nonnegligible side effects and limited efficacy of clinical treatment limit their biomedical applications. Engineered bacteria for therapeutic applications ideally need to avoid their accumulation in normal organs and possess potent antitumor activity. Here, we show that macrophage-mediated tumor-targeted delivery of Salmonella typhimurium VNP20009 can effectively reduce the toxicity caused by administrating VNP20009 alone in a melanoma mouse model. This benefits from tumor-induced chemotaxis for macrophages combined with their slow release of loaded strains. Inspired by changes in the tumor microenvironment, including a decrease in intratumoral dysfunctional CD8⁺ T cells and an increase in PDL1 on the tumor cell surface, macrophages were loaded with the engineered strain VNP-PD1nb, which can express and secrete anti-PD1 nanoantibodies after they are released from macrophages. This novel triple-combined immunotherapy significantly inhibited melanoma tumors by reactivating the tumor microenvironment by increasing immune cell infiltration, inhibiting tumor cell proliferation, remodeling TAMs to an M1-like phenotype and prominently activating CD8⁺ T cells. These data suggest that novel combination immunotherapy is expected to be a breakthrough relative to single immunotherapy.

【Objective】 To study the application effect of gel adsorbent tank in the production of human prothrombin complex concentrate(PCC). 【Methods】 Six batches of PCC were produced from 1000 L cryoprecipitated plasma, using the same gel twice for adsorption within the tank.The number of gel repeated application was examined by retrospective confirmation, and the adsorption rate, specific activity and residue of finished virus inactivation reagent were determined before and after adsorption. 【Results】 All 6 batches of PPC, produced by the same gel, satisfied quality criteria. Both PPC solution and the gel presented good color. The average activities of coagulation Factors Ⅱ, Ⅶ, Ⅸ and Ⅹ of six batches of PCC were 118.2%, 157.0%, 140.5% and 176.8%, respectively. The The adsorption capacity of coagulation factor Ⅱ, Ⅸ and Ⅹ were both 100% in the first and second adsorption, while coagulation factor Ⅶ were 75% and 81%, respectively. The average specific activity of coagulation factor Ⅸ was 0.7 IU/mg. The average residues of polysorbate 80 and tributyl phosphate products were 0 μg/mL and 33 μg/mL, respectively. The same batch of gel can be repeatedly used up to 6 times during the PCC process. 【Conclusion】 The gel adsorption tank presents good application value in the production of PCC, which can realize process amplification and automatic control.

Objective To explore the application and effectiveness of one-staged or two-staged hybrid minimally invasive surgical and transcatheter ablation for long-standing persistent atrial fibrillation(LSPAF).Methods From Jun 2015 to Dec 2017,a cohort of 56 patients[18 female,mean age of(59.1 ±6.9) years] with long-standing persistent atrial fibrillation underwent one-staged(30 cases) or two-staged(26 cases) hybrid minimally invasive surgical and transcatheter ablation.Mean AF duration was(5.9 ± 3.0) years.Mean left atrial diameter was(45.4 ± 4.2) mm.Mean CHA2DS2-VASc score was 2.3 ± 1.2.Fourteen cases had a history of prior catheter ablation.All patients underwent continuous 24-hour or 48-hour holter monitoring at 3 months,6 months,1 year and yearly thereafter.Results All patients successfully underwent one-staged or two-staged hybrid minimally invasive surgical and transcatheter ablation.During ablation,LSPAF was terminated in 80.0％ (24/30) with one-staged hybrid ablation and 84.6％ (22/26) with two-staged hybrid ablation.At a mean follow-up of(20.3 ± 8.2) months,89.3％ (50/56) patients maintained sinus rhythm.Among them,86.7％ (26/30) patients with one-staged hybrid ablation maintained sinus rhythm,and 92.3％ (50/56) patients with two-staged hybrid ablation maintained sinus rhythm.Six patients with recurrent AF continued to receive warfarin and amiodarone drug therapy.No death or cerebrovascular events occurred.No patient required permanent pacemaker implantation.Conclusion One-staged or two-staged hybrid minimally invasive surgical and transcatheter ablation could be safely and effectively applied to the treatment of LSPAF.The early and midterm outcomes were satisfactory.

Objective To explore the mechanisms of ligament of Marshall (LOM) initiat and sustain atrial fibrillation (AF).Methods The electrophysiologic properties of canine LOM were investigated using multipolar catheter mapping(normal canines,n =4,group A;AF canines,n =5,group B).The programmed stimulation were performed in the LOM,PV-left atrium(LA)junction and LA,respectively.Activations maps of LOM were analyzed from episodes of spontaneous onset of AF and initiation of induced AF by a single extrastimulus.The effectives refractory period of each part was compared and statistically analyzed among three parts in each group and between the two groups.LOM were cutted with surgical incision technology.The inducing rate of AF and the mapping rate of double potential and fragmented electrocardiogram were compared and statistically analyzed pro and post isolation of LOM.Results The incidence of abnormal potential of LOM in the two groups was significantly different(P ＜0.01),re-entry cycle(group A 25％ vs.B group 80％),tachycardia(group A 25％ vs.B 100％),double potential(group A 25％ vs.group B 80％),fragmentation potential(group A 25％ vs.group 80％).There was a significant difference in the rate of LOM tachycardia induction before and after LOM intervention in group B (P ＜ 0.05,before 100％ vs.after 20％).Conclusion There are two possible mechanisms of LOM involved in the occurrence and maintenance of AF:one is that LOM induces AF through spontaneous excitation,the other is that LOM participates in the reentry of left atrium and pulmonary vein in the form of bypass to induce and maintain AF.

Objective: To evaluate the effect of computer-assisted design based on three-dimensional reconstruction technique on the reduction accuracy of tibial and fibular fractures with Taylor external fixation. Methods: A retrospective review was conducted on the clinical data of 69 patients who had tibia and fibula fractures treated with Taylor external fixation in department of orthopedic trauma of Tianjin Hospital from January 2016 to January 2018 to compare the residual deformity after fracture reduction between computer-assisted design method (experimental group) and the standard measurement method (control group). The frontal and lateral tibia and fibula X-ray of all the affected limbs were taken. In experimental group, all the patients took bilateral tibial CT tomography, and then DICOM format documents were input into the Mimics 17.1 software and got three-dimensional models of targeted bone and external fixation ring. After that the visual image matching was performed between external fixation ring three-dimensional reconstruction model and the standard model and also between the affected limb and the contralateral limb. Then the reduction trajectory plan of bone broken end and the position of external fixation ring were obtained. The STL files were input to Solid Works software and got the length of six rods to adjust the Taylor external fixation. In control group, the films were measured by Coreldraw X7 X-ray measurement software and the parameters were input in Taylor Spatial Frame system software. And then six calibrated threaded rods were adjusted according to the prescription of the software. Finally, all the patients took the X-ray films again to evaluate the degree of residual displacement. Skew distributional data are indicated with M(Q_R), and method of non-parameter was used to analyze variances between groups. Results: All patients had better fracture reduction and achieved functional reset criteria. In the control group, the amount of displacement and angle residual aberration (improvement) in the frontal and lateral radiographs were 0.50(2.30)mm(90%), 0.00(0.85)mm(100%)and 0.00°(1.50°)(100%), 0.00°(0.00°)(100%), respectively. In the control group, the amount of displacement and angle residual aberration (improvement) in the frontal and lateral radiographs were 1.40(3.28)mm(69%), 2.15(4.27)mm(46%)and 1.15°(1.85°)(73%), 0.80°(2.10°)(67%). The positive and lateral angles and lateral displacements in the two groups were significantly different(P<0.05), but there was no statistically significant difference in positive displacement (P=0.099). Conclusion Both computer-assisted design method and the standard measurement method have satisfactory reduction effect, but computer-assisted design can accurately correct fracture deformity, which is good for fracture healing and functional recovery of affected limb.

Objective To investigate the protective effects of antioxidant taurine plus metoprolol on the blood pressure(BP)and blood vessel function of elderly spontaneously hypertensive rats(SHR).Methods SHRs were divided into three groups (6 rats,each):metoprolol group (100 mg · kg-1 · d-1,intragastric administration);taurine group (200 mg · kg-1 · d-1,intraperitoneal injection);taurine plus metoprolol group(metoprolol 100 mg· kg-1 · d-1,intragastric administration ± taurine 200 mg· kg-1 · d-1,intraperitoneal injection).The control group[6 Wistar-Kyoto(WKY) rats]was treated with the same volume of sterile normal saline on the same schedule in intragastric administration and intraperitoneal injection.Blood pressure variability(BPV),diurnal variation of BP,the level of glutathion peroxidase (GSH-Px),malonaldehyde (MDA) and the aorta GSTM1 enzyme expression were evaluated before and 14 days after treatment.Results The serum GSH-Px activities were higher in metoprolol group[(2 759.8 ± 117.6) kU/L],taurine group [(2 848.0 ± 280.2) kU/L] and taurine plus metoprolol group[(3 052.8±283.7)kU/L]than in control group[(2 368.0± 60.4) kU/L] (all P＜0.05).Fourteen days after treatment,MDA level was significantly lower in taurine group[(9.5±0.7)ng/L,P＜0.01]than in control group[(13.7±1.5)ng/L].However,there was no statistical difference in MDA level between metoprolol group/taurine plus metoprolol group and control group.Forty weeks after treatment with taurine,GSTM1 protein expression was increased,but it had no statistical difference.Conclusions The combined antioxidant taurine and metoprolol can effectively decrease BPV of elderly SHRs,in which the antioxidant effect might be associated with elevated GSTM1 protein expression.

Objective To investigate the alteration of C/EBP α,C/EBP β and endoplasmic reticulum stress (ERS) related molecules (IRE1α and sXBP1) expression in pancreatic tissues in rats with hypertriglyceridemia related acute pancreatitis.Methods Ninety six Sprague Dawley (SD) rats were divided into 4 groups:control group,hypertriglyceridemia (HTG) group (n =24,fed with high fat diet for 2 weeks),AP group (n =24),HTG + AP group (n =24),and AP was induced by peritoneal injection of cerulein.The rats were sacrificed at 3,6,9,24 h after AP induction,respectively.The pathological changes of the pancreatic tissues were observed and scored by HE staining.Plasma levels of IL-1β,IL-6 and TNF-α were measured by ELISA.The expression of IRE1α,sXBP1,C/EBPoα,C/EBPβ mRNA were analyzed by real time PCR.The expressions of IRE1α,sXBP1,NF-kB,C/EBPα and C/EBPβ protein were determined by Western Blot.The expressions of C/EBPα and C/EBPβ proteins were also determined by immunohitochemistry.Results After two weeks of high fat diet,serum levels of triglyceride(TG) and total cholesterol (TC) in HTG group,HTG + AP group were much higher than those of the control group,and the difference was statistically significant (P ＜ 0.05).The pancreatic tissue injury was more severe in HTG + AP group,particularly at 9 h (P ＜ 0.05).And plasma IL-1β,IL-6 and TNF-α levels were also much higher in HTG + AP group when compared with that of AP group,the differences were all significant at 9 h (P=0.011;P=0.034;P =0.027).After AP induction,IRE1,sXBP1,C/EBP and C/EBPβ mRNA began to be up-regulated at 3 h,and IRE1 mRNA reached the highest level at 24 h,sXBP1 mRNA at 9 h,while C/EBP and C/EBPβ mRNA reached the highest level at 6 h.Compared with AP group,IRE1,sXBP1,C/EBP and C/EBPβ mRNA levels were much higher in HTG + AP group.In addition,as to IRE1 and sXBP1 mRNA,the difference was significant at 3,6,9,24 h,and C/EBP mRNA at 6,9,24 h,C/EBPβ mRNA at 6 and 9 h (P ＜ 0.05).After AP induction,IRE1α,sXBP1 and NF-kB proteins in the pancreatic tissue began to be up-regulated at 3 h,and all reached the highest level at 9 h.IRE1α,sXBP1 and NF-kB proteins were up-regulated more obviously in HTG + AP group,and the up-regulation in HTG + AP group was higher than that in AP group,and the high expressions of C/EBPα and C/EBPβ proteins could only be detected at 6 and 9 h in the HTG + AP group,while there was no expression detected in AP group.Conclusions C/EBPα,C/EBPβ,IRE1α and sXBP1 may be involved in the pathogenesis of HTG related AP,and IRE1α/sXBP1 pathway and C/EBPoα,C/EBPβ may mediate the pathologic injury and inflammation process of HTG related AP.