Objective:To discuss the clinical application value of echocardiography in evaluating the early outcomes of transcatheter aortic valve replacement(TAVR)via the transapical approach,and to clarify the role of echocardiography in assessing the efficacy of the surgery.Methods:The clinical data of 85 patients who received J-Valve prosthetic valves via the transapical TAVR were retrospectively analyzed.The patients were divided into AS group(simple aortic stenosis,n=20),AR group(simple aortic regurgitation,n=37),and AS&AR group(aortic stenosis with regurgitation,n=28).Echocardiographic examination was performed on all the patients before operation,1 week after operation,3 months after operation,and 6 months after operation.The parameters including left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),interventricular septal thickness(IVST),left ventricular posterior wall thickness(LVPWT),aortic valve peak flow velocity(AV Vmax),aortic valve mean transvalvular pressure gradient(AV PGmean),and paravalvular leak(PVL)width were measured to evaluate the cardiac function and the function of the prosthetic valve;the occurrence of postoperative complications of the patients in various groups was also analyzed.Results:J-Valve prosthetic valves were successfully implanted in all 85 patients.There were no significant differences in age,gender,New York Heart Association(NYHA)heart function classification,history of hypertension,history of diabetes,history of hyperlipidemia,and history of coronary artery disease among various groups befor operation(P＞0.05),ensuring comparability.Compared with before operation,1 week after operation,the AV Vmax and AV PGmean of the patients in AS group and AS&AR group were decreased(P＜0.05);there were no significant differences in various parameters of the patients in AR group(P＞0.05).Compared with before operation,3 months after operation,the LVEF and LVFS of the patients in AS group were increased(P＜0.05),while the AV Vmax and AV PGmean were decreased(P＜0.05);the LVEDV and LVESV of the patients in AR group were decreased(P＜0.05),while the LVEF and LVFS were increased(P＜0.05);the LVEDV,LVESV,AV Vmax,and AV PGmean of the patients in AS&AR group were decreased(P＜0.05),while the LVEF and LVFS were increased(P＜0.05).Compared with before operation,LVEDV,LVESV,IVST,and LVPWT of the patients in all three groups 6 months after operation were decreased(P＜0.05),while LVEF and LVFS were increased(P＜0.05);the AV Vmax and AV PGmean of the patients in AS group and AS&AR group were decreased(P＜0.05);the AV PGmean of the patients in AR group was decreased(P＜0.05).The postoperative complications included 3 cases of permanent pacemaker implantation(2 cases in AS group,1 case in AR group),1 case of stroke(in AS group),and 13 cases of PVL(4 cases in AS group,5 cases in AR group,4 cases in AS&AR group).No deaths occurred during follow-up.Conclusion:Echocardiography can accurately and quantitatively evaluate early changes in cardiac function and the functional state of prosthetic valves after transapical TAVR,providing objective evidence for evaluating surgical outcomes and postoperative complications.

Objective To identify genetic regulators of ionizing radiation(IR)sensitivity through clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease 9(Cas9)genome-wide screening.Methods A specialized single guide RNA(sgRNA)library was developed targeting 987 stress-response regulatory genes identified through Kyoto Encyclopedia of Genes and Genomes(KEGG),Reactome and gene ontology(GO)databases,followed by construction of sgRNA plasmids and packaging into a lentiviral library.Using colon adenocarcinoma Caco-2 cells as a model system,the Cas9-stable transgenic line was established via lentiviral transduction and antibiotic selection.Library-transduced cells underwent puromycin selection,followed by γ-irradiation(dose optimized via preliminary experiments).Post-irradiation phenotypic selection was conducted after 14 days,with subsequent next-generation sequencing of surviving cell populations to identify enriched/depleted sgRNAs.Candidate genes were functionally validated through orthogonal assays:cell counting kit-8(CCK-8)proliferation analysis,clonogenic survival assays and flow cytometric quantification of reactive oxygen species(ROS)and apoptotic markers.Results The optimized screening platform identified 281 radiation response genes(165 radiosensitive and 116 radioprotective candidates).Functional validation revealed Bcl2-associated athanogene 3(BAG3)knockdown significantly enhanced radioresistance.Proliferation was increased 1.2-1.5 fold,clonogenic survival improved 1.5-2.0 fold,and ROS was reduced by 13％-25％coupled with 32％-73％apoptosis attenuation compared to control groups.Conclusion The integrated CRISPR/Cas9 screening platform effectively identifies novel radiation response regulators,as evidenced by the discovery of BAG3 as a critical radiosensitivity determinant.This high-throughput functional genomics approach provides a robust methodology for systematically mapping molecular determinants of cellular radiation response,with potential applications in both mechanistic studies and therapeutic target discovery.

OBJECTIVE To study the effects of methimazole on the urinary metabolomics of hyperthyroidism rats， and to preliminarily investigate its possible mechanism. METHODS Thirty SD rats were randomly divided into control group， model group and methimazole group， with 10 rats in each group. Except for the control group， the rats in the other two groups were given Levothyroxine sodium tablets 160 mg/kg by intragastric administration for 15 days； at the same time， methimazole group was additionally given methimazole 3.6 mg/kg daily by intragastric administration every day. The basic condition of the rats was observed， and the body weight and anal temperature were measured. After the last medication， the serum levels of triiodothyronine （T3）， tetraiodothyronine （T4）， free triiodothyronine （FT3）， free tetraiodothyronine （FT4）， and thyroid stimulating hormone （TSH） were determined； 24-hour urine was collected on the 15th day after administration. UPLC-TOF-MS was used to analyze the urine metabolomics of rats. Principal component analysis and orthogonal partial least squares-discriminant analysis were used to screen out related differential metabolites， and potential metabolic pathways were analyzed by using HMDB and KEGG. RESULTS Compared with the control group， the rectal temperature， serum levels of T3， T4， FT3 and FT4， the expressions of differential metabolites sebacic acid， cholic acid 3-O-glucuronic acid and N6， N6， N6-trimethyl-L-lysine in urine were significantly up-regulated， while body weight， serum level of TSH， the expressions of deoxycytidine and 2-oxo-4-methylthiobutanoic acid in urine were significantly down-regulated （P＜0.01）. Compared with model group， above indexes of rats were reversed significantly in methimazole group （P＜0.01 or P＜0.05）. Above five differential metabolites were mainly involved in four signaling pathways: pentose and glucuronate interaction， lysine degradation， cysteine and methionine metabolism， and pyrimidine metabolism. CONCLUSIONS Methimazole might improve hyperthyroidism by modulating the four pathways of pentose and glucuronate interaction， lysine degradation， cysteine and methionine metabolism， and pyrimidine metabolism.

Objective: To investigate the relationship between monokine induced by interferon⁃gamma (MIG) level and coronary slow flow phenomenon ( CSFP) . Methods: 80 patients diagnosed with CSFP and 54 patients with normal CAG were selected as the CSFP group and no⁃CSFP group respectively in this study. Coronary slow flow was determined quantitatively by thrombolysis in myocardial infarction (TIMI) frame count (TFC) method. The clinical characteristics and biochemical indexes , including serum CD40L and Interferon⁃γ (IFN⁃γ) , monokine induced by interferon⁃gamma (MIG) levels were measured , and the relationship between interferon⁃γ induced monocyte level and CSFP were analyzed. Results: The serum levels of CD40L , IFN⁃γand MIG in the CSFP group were higher than those in the no⁃CSFP group ( P = 0. 001) . The MIG levels were positive correlated with mean TFC ( r =0. 879 ,P = 0. 009) . Multivariate logistic regression analysis showed that MIG was an important risk factor for CSFP (β = 0. 874 ,P = 0. 011) . The ROC curve analyses indicated that the MIG levels had diagnostic value in patients with CSFP , the area under the curve ( AUC) was 0. 793 , the sensitivity was 0. 79% and the specificity was 76. 0% , and 95% CI 0. 714 - 0. 872. Conclusion Chemokine CD40L , IFN⁃ γ and MIG may be involved in the process of vascular inflammation and arteriosclerosis. MIG is an important influencing factor of CSFP and participated in the occurrence and development of CSFP.

Tumor is a serious threat to human health. At present, surgical resection, chemoradiotherapy, targeted therapy and immunotherapy are the main therapeutic strategies. Monoclonal antibody has gradually become an indispensable drug type in the clinical treatment of cancer due to its high efficiency and low toxicity. Phage antibody library technology (PALT) is a novel monoclonal antibody preparation technique. The recombinant immunoglobulin variable region of heavy chain (VH)/variable region of light chain (VL) gene is integrated into the phage vector, and the antibody is expressed on the phage surface in the form of fusion protein to obtain a diverse antibody library. Through the process of adsorption-elution-amplification, the antibody library can be screened to obtain the antibody molecule with specific binding antigen as well as its gene sequence. PALT has the advantages of short antibody production cycle, strong plasticity of antibody structure, large antibody yield, high diversity and direct production of humanized antibodies. It has been used in screening tumor markers and preparation of antibody drugs for breast cancer, gastric cancer, lung cancer and liver cancer. This article reviews the recent progress and the application of PALT in tumor therapy.
Humans ; Bacteriophages/genetics* ; Immunoglobulin Variable Region/genetics* ; Gene Library ; Antibodies, Monoclonal/therapeutic use* ; Immunotherapy ; Peptide Library

Objective To investigate the situation and the causes of neonatal death in Henan Province.Methods This study retrospectively analyzed the clinical data of 277 neonates who died at 18 hospitals in Henan Province in 2017.Distribution and causes of neonatal deaths,differences between perinatal conditions of premature and term/post-term infants,causes of early (＜ 7 d) and late (7-28 d) neonatal deaths and the differences in neonatal death cases between Maternal and Child Health Care Hospitals and General/Children's Hospitals were analyzed.We used t,rank-sum and Chi-square test (or corrected Chi-square test,or Fisher's exact test) for statistical analysis.Results (1) A total of 50 993 newboms were admitted to the 18 hospitals in 2017,297 of which died with a mortality of 5.82‰.After excluding 20 cases with uncertain birth or maternal pregnancy history or clinical data,277 cases with complete data were analyzed.Among them,168 (60.6％) were preterm neonates and 109 (39.4％) were term/post-term ones.Early and late neonatal deaths accounted for 74.0％ (205 cases) and 26.0％ (72 cases),respectively.(2) The top five causes of neonatal deaths were infection (78 cases,28.2％),asphyxia (54 cases,19.5％),neonatal respiratory distress syndrome (NRDS,33 cases,11.9％),severe congenital malformations (26 cases,9.4％) including cyanotic congenital heart diseases,digestive malformations,airway malformations and neural tube defects and pulmonary hemorrhage (23 cases,8.3％).Among them,the top three causes of early neonatal deaths were asphyxia (48 cases,23.4％),infection (43 cases,21.0％) and NRDS (33 cases,16.1％),while the main causes of late neonatal deaths were infection (35 cases,48.6％),major congenital malformations (9 cases,12.5％) and chromosome abnormities/inherited metabolic diseases (7 cases,9.7％).(3) Maternal complications during pregnancy accounted for 79.1％ (219 cases) and the predominant types were pregnancy-induced hypertension (43 cases,19.6％),followed by infection (36 cases,16.4％),placental-related conditions (32 cases,14.6％),gestational diabetes mellitus (23 cases,10.5％),hypothyroidism (20 cases,9.1％),fetal distress (18,8.2％),twin-twin transfusion syndrome (10 cases,4.6％) and cholestasis syndrome (9 cases,4.1％).(4) Compared with the term/post-term cases,the preterm cases had higher proportions of multiple births [27.4％ (46/168) vs 6.4％ (9/109),x2=14.016,P ＜ 0.05],assisted reproduction [7.1％ (12/168) vs 0.9％ (1/109),x2=4.421,P ＜ 0.05] and maternal hypertensive disorders of pregnancy [21.4％ (36/1 68) vs 6.4％ (7/109),x2=11.353,P ＜ 0.05],infection [16.7％ (28/168) vs 7.3％ (8/109),x2=4.295,P ＜ 0.05] and twin-to-twin transfusion syndrome [6.0％ (10/168) vs 0.0％ (0/109),x2=6.707,P ＜ 0.05].(5) Among all the early neonatal deaths,preterm cases had a higher incidence of NRDS than term/post-term neonates [20.3％ (27/133) vs 8.3％ (6/72),x2=1 1.937,P ＜ 0.05],but lower incidence of meconium aspiration syndrome (MAS),severe congenital malformations and chromosome abnormalities/inherited metabolic diseases [0.8％ (1/133) vs 5.6％ (4/72),x2=4.508;3.8％ (5/133) vs 16.7％ (12/72),x2=10.233;1.5％ (2/133) vs 6.9％ (5/72),~=4.172;all P ＜ 0.05].Among the late neonatal deaths,the incidence of severe intracranial hemorrhage in preterm infants was higher than that in term/post-term neonates [7.1％ (3/42) vs 0.0％ (0/30),x2=2.205,P ＜ 0.05].(6) Compared with the cases in General/Children's Hospitals,those in Maternal and Child Health Care Hospitals showed a higher proportion of preterm neonatal deaths [67.3％ (105/156) vs 52.1％ (63/121),x2=6.010,P ＜ 0.05],younger gestational age [(32.8±5.3) weeks vs (34.6±4.9) weeks,t=3.072,P ＜ 0.05],lower birth weight [(2 132.6± 1 014.5) g vs (2 409.4±987.3) g,t=-2.513,P ＜ 0.05],and higher average age of death [M(P25-P75),3 (1-8) d vs 2 (1-4) d,Z=3.710,P ＜ 0.05].Conclusions Neonatal death occurs mainly within one week after birth in those with maternal complications.Late preterm deaths and term/post-term cases account for nearly half of total neonatal deaths.The causes of death for preterm and term/post-term newborns vary with postnatal age.Infection,asphyxia and severe congenital malformations are important causes of neonatal deaths.

Objective To assess the value of transesophageal echocardiography (TEE) in left atrial appendage (LAA) closer with Amplatzer Cardiac Plug (ACP).Methods Consecutive 32 atrial fibrillation patients (CHADS2≥1) with high risk bleeding underwent LAA occlusion with ACP LAA occlusion device under the guidance of TEE.Measurements of LAA anchoring area diameter (AAD) and LAA anatomical orifice diameter (AOD) including maximum,minimum values,and LAA depth on 2 dimentional TEE (2D TEE) were conducted before closer device implantation.The outcomes of LAA occlusion were analyzed.Results Among 32 patients,27 cases achieved successful LAA occlusion,including 2 cases with peripheral leakage ≤5 mm,and 5 cases failed occlusion.Among 5 failed closed patients,3 cases with LAA AAD≥ 30 mm,1 case with LAA of short depth,and 1 case with anatomical variation of LAA of low position that access sheath could not be positioned in the LAA.LAA AAD maximum,minimum and LAA depth were (25.9±4.9)mm,(20.0±3.8)mm,(31.0±5.6)mm,respectively,and LAA AOD maximum,minimum diameters were (26.2±6.2)mm,(19.4±4.3)mm,respectively.Among 10 cases with LAA AAD≥30 mm,7 cases achieved successful LAA occlusion,but 3 cases failed.The implanted device diameter was (26.4±3.8)mm,and device compression rate was (7.6±5.5)%.The coefficient of correlation between device diameter and large LAA AAD and AOD is 0.770 and 0.717,respectively.There was no complication but 1 case with pericardial effusion.Conclusions Two dimentional TEE measurements of LAA have clinical guiding significance in the selection of proper size of ACP LAA occluder.The AAD of 2D TEE has the good correlation with ACP occluder′s size,the AADs are important factors which affect the success of LAA occlusion.

Objective To investigate and optimize the penetration enhancers of Xiaochuan emplastrum. Methods Franz diffusion cell was employed with isolated mice abdominal skin as barrier. The accumulating osmotic quantity per unit area and penetrating absorption rate of Sinapine thiocyanate were determinated by HPLC method. The penetration enhancers were selected and the ratio was determined. Results Combination of azone and propylene glycol were better than other kinds of enhancers for penetration effect, the ratio of propylene glycol and azone was 2:1. Dosage of azone and propylene glycol was finally optimized to 5% of prescription dosage.Under these conditions, cumulative permeation quantity of Sinapine thiocyanate was 369.59 μg·(cm2)-1, penetration rate of Sinapine thiocyanate was 14.19 μg·(cm2)-1·h-1 and enhancing rate was 3.19. Conclusion The ratio of propylene glycol and azone was 2:1,dosage of azone and propylene glycol was 5% of prescription dosage, which has a significant penetration effect and can be used as the penetration enhancer of Xiaochuan emplastrum.

Objective To evaluate right ventricular (RV)systolic function in type-2 diabetes mellitus (T2DM)patients.Methods Fifty T2DM patients and fifty normal controls were included in the study and underwent echocardiographic examinations.The following parameters were measured:1 ) Right heart dimensions,pulmonary artery (PA)diameter,pulmonary acceleration time (AT)and PA systolic pressure (PASP);2)RV systolic function:RV fractional area change (RVFAC),tissue Doppler-derived tricuspid lateral annular systolic velocity (S'),tricuspid annular plane systolic excursion (TAPSE),longitudinal strain of six RV segments by 2-dimensional speckle tracking imaging (2D-STI);3 )RV diastolic function:E,A ratio of the tricuspid inflow spectrum (E/A),E,E'(peak early diastolic velocity of the tricuspid annulus) ratio (E/E');4)RV Tei index.Results Statistic analysis showed that T2DM patients had thicker RV walls,wider PAs and shorter AT than the control group (P =0.000,0.001 and 0.000),while their right heart chamber sizes and PASP remained unchanged.Among systolic parameters,absolute values of RV longitudinal strain at the lateral wall-mid (lat-m),septum-mid (sep-m)and septum-basal (sep-b)segments were significantly lower in the diabetic group than the control group (P =0.001 ,0.000 and 0.005),whereas strain of the other three RV segments and RVFAC,TAPSE.S'were not significantly different.Moreover, E/A,E/E'and Tei index were all significantly different between the two groups (P = 0.000,0.000 and 0.006),indicating declined diastolic and general function of RV in the T2DM group.Conclusions RV myocardial strain by 2D-STI is more sensitive in detecting RV systolic dysfunction than TAPSE,S' and RVFAC.Among the six segments of RV walls,lat-m,sep-m and sep-b are better locations for 2D-STI than the other three.

Objective To evaluate the role of real-time three-dimensional transesophageal echocardiography(RT-3D TEE)in left atrial appendage (LAA)occlusion.Methods Consecutive 10 atrial fibrillation (AF)patients (CHADS2 ≥ 2 )with high risk bleeding underwent LAA occlusion under the guidance of TEE.The LAA orifice shape and characteristics of lobes were assessed,the size of LAA with RT-3D TEE wee measured before closer implanation,and the position of the LAA occlusion device were evaluated by RT-3D TEE.The correlational analysis between LAA diameter and occluder size was conducted.Results Among 10 patients,the test results revealed 8 cases with complete LAA occlusion and 1 case with incomplete occlusion,and 1 case with failed occlusion.Five cases showed approximate round LAA ostium,and the other 5 showed approximate oval ostium.The average number of LAA lobes were 2.2±0.7. LAA ostium long diameter were larger by 3D TEE compared with 2D TEE[(21 .8±5.1)mm vs (20.8±4.1) mm],and ostium short diameter were smaller by 3D TEE compared with 2D TEE [(16.1 ± 3.0 )mm vs (1 7.0±2.6)mm],however there were no significant differences between 2D and 3D TEE measurements,and the mean ostium diameter and LAA depth were comparable between two methods.LAA ostium long diameter,short diameter,average diameter and LAA depth assessed by 3D TEE and 2D TEE showed good correlation with occluder diameter (3D TEE:r =0.719,0.690,0.791 ,0.71 1 ,and P =0.029,0.040,0.01 1 , 0.032,respectively;2D TEE:r = 0.887,0.894,0.932,0.896,and P = 0.001 ,0.001 ,0.000,0.000, respectively).LAA occlusion device position assessed by RT-3D:6 cases with appropriate position, acceptable position with 2 cases,and 1 case with malposition.Conclusions RT-3D TEE can play important role in evaluating the morphology of LAA,accurately judging LAA ostium shape and size and position of the occlusion device.