Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective:To explore the impact of transcatheter edge-to-edge repair (TEER) devices on mitral valve regurgitant flow convergence post-procedure using computational fluid dynamics(CFD), and to seek solutions for accurately measuring effective regurgitant orifice area(EROA) after TEER.Methods:Multimodal fusion was conducted based on preoperative cardiac CT images and intraoperative three-dimensional transesophageal echocardiography(3DTEE) of 33 patients with mitral valve regurgitation undergoing TEER at Renmin Hospital of Wuhan University from January 2020 to August 2023. Using this data, CFD models of mitral valve regurgitation post-TEER, including with and without the TEER device, were constructed. The distance (D) from the midpoint of the mitral regurgitation orifice to the TEER device was measured. The proximal isovelocity surfice area(PISA) radius with and without the TEER device was measured, and the corresponding EROA1 and EROA2 based on this was calculated. The EROA correction factor CC=EROA2/EROA1 was calculated.Results:A total of 42 sets of CFD models with mild or greater residual mitral regurgitation, both with and without the TEER device, and 50 sets of PISA were obtained. Based on the relative position of PISA to the TEER device, four types of PISA were observed: Type 1: PISA away from the TEER device (D>R, 14 cases), with a CC of 0.93±0.07; Type 2: PISA adjacent to the TEER device (D

Objective:To predict the mechanism of Danggui Buxue Decoction for anti-myocardial ischemia-reperfusion injury and "treating different diseases with the same method" in ischemic stroke based on network pharmacology and molecular docking.Methods:The active components and targets of Danggui Buxue Decoction were screened by retrieving the database of TCMSP and literature; the corresponding targets of myocardial ischemia-reperfusion injury and ischemic stroke were found by OMIM and GeneCards database; the intersection targets of Danggui Buxue Decoction and disease were obtained by using Venny diagram, and the common target network and protein-protein interaction network were constructed by Cytoscape 3.7.1 software and STRING database. The GO and KEGG pathways were enriched by David Database, and the Bio GPS database was used to obtain the tissue distribution information of the key targets. The molecular docking technology was used to verify the results.Results:There were 21 active components in Danggui Buxue Decoction, 181 effective targets and 93 cross targets with diseases. The key components were quercetin, Kaempferol, β-sitosterol, formononetin and isorhamnetin. The key targets were AKT1, TNF, IL6, IL-1β and VEGFA. The enrichment results showed that the main action pathways were fluid shear force and arteriosclerosis, lipid and arteriosclerosis, AGE-RAGE signal pathway in diabetic complications, and the core targets were mainly located in the medullary cells, dendritic cell, smooth muscle, prostate, thyroid and other tissues. The results of molecular docking showed that quercetin had the best binding effect to IL-1β, while isorhamnetin had the best binding effect to IL-1β.Conclusion:Danggui Buxue Decoction is against myocardial ischemia-reperfusion injury and ischemic stroke through hemodynamics, lipid metabolism, inflammatory reaction, oxidative stress, immune reaction and cell apoptosis, plays the role of "treating different diseases with the same method".

Objective:To explore the prognostic predictive value of deep neural network (DNN) assisted myocardial contrast echocardiography (MCE) quantitative analysis of ST-elevated myocardial infarction (STEMI) patients after successful percutaneous coronary intervention(PCI).Methods:A retrospective analysis was performed in 97 STEMI patients with thrombolysis in myocardial infarction-3 flow in infarct vessel after primary PCI in Renmin Hospital of Wuhan University from June to November 2021. MCE was performed within 48 h after PCI. Patients were followed up to 120 days. The adverse events were defined as cardiac death, hospitalization for congestive heart failure, reinfarction, stroke and recurrent angina. The framework consisted of the U-net and hierarchical convolutional LSTMs. The plateau myocardial contrast intensity (A), micro-bubble rate constant (β), and microvascular blood flow (MBF) for all myocardial segments were obtained by the framework, and then underwent variability analysis. Patients were divided into low MBF group and high MBF group based on MBF values, the baseline characteristics and adverse events were compared between the two groups. Other variables included biomarkers, ventricular wall motion analysis, MCE qualitative analysis, and left ventricular ejection fraction. The relationship between various variables and prognosis was investigated using Cox regression analysis. The ROC curve was plotted to evaluate the diagnostic efficacy of the models, and the diagnostic efficacy of the models was compared using the integrated discrimination improvement index (IDI).Results:The time-cost for processing all 3 810 frames from 97 patients was 377 s. 92.89% and 7.11% of the frames were evaluated by an experienced echocardiographer as "good segmentation" and "correction needed". The correlation coefficients of A, β, and MBF ranged from 0.97 to 0.99 for intra-observer and inter-observer variability. During follow-up, 20 patients met the adverse events. Multivariate Cox regression analysis showed that for each increase of 1 IU/s in MBF of the infarct-related artery territory, the risk of adverse events decreased by 6% ( HR 0.94, 95% CI =0.91-0.98). There was a 4.5-fold increased risk of adverse events in the low MBF group ( HR 5.50, 95% CI=1.55-19.49). After incorporating DNN-assisted MCE quantitative analysis into qualitative analysis, the IDI for prognostic prediction was 15% (AUC 0.86, sensitivity 0.78, specificity 0.73). Conclusions:MBF of the area supplied by infarct-related artery after STEMI-PCI is an independent protective factor for short-term prognosis. The DNN-assisted MCE quantitative analysis is an objective, efficient, and reproducible method to evaluate microvascular perfusion. Assessment of culprit-MBF after PCI in STEMI patients adds independent short-term prognostic information over qualitative analysis.It has the potential to be a valuable tool for risk stratification and clinical follow-up.

Self-efficacy can affect the confidence of adolescent patients with chronic diseases in coping with disease and management, and then affect their disease management and health behavior. This paper introduced the concept of self-efficacy of adolescent patients with chronic diseases, and summarized self-efficacy scale for adolescent patients with chronic diseases from aspects of development, application scope and the reliability and validity, to provide reference for clinical evaluation of self-efficacy level of adolescent patients with chronic diseases during treatment and formulation of targeted intervention plan.

Objective:To investigate the effect of usage of transthoracic echocardiography(TTE) on the prognosis of patients after acute kidney injury (AKI) in intensive care unit (ICU).Methods:The clinical data of patients with AKI in the Medical Information Mart for Intensive Care (MIMIC-Ⅲ v1.4) database was collected retrospectively, and the patients were divided into TTE group (with TTE within 24 hours of AKI diagnosis) and No-TTE group (without TTE examination or first TTE examination was more than 24 hours after AKI diagnosis). Propensity score matching (PSM) was utilized to balance the baseline variables between the two groups and Cox regression analysis was used to evaluate the independent risk factors for 28-day all-cause mortality (the primary outcome). Moreover, after PSM, the effects of TTE usage on the second outcomes (including the volumes of intravenous fluid and urine output in the first, second and third 24-hour after the diagnosis of AKI; the total number of mechanical ventilation-free days, renal replacement therapy-free days and vasopressor-free days within 28 days after ICU admission; use of diuretics after the diagnosis of AKI; reduction in serum creatinine within 48 hours after the diagnosis of AKI; and the length of ICU stay and hospital stay) were also evaluated.Results:Among 23 945 eligible AKI patients, 3 365 patients (14.1%) patients received TTE within 24 hours after the diagnosis of AKI and finally there were 3 361 patients in TTE group and No-TTE group included in this study after PSM based on the ratio of 1∶1. After PSM, all variables in the two groups were well balanced (standardized mean difference<0.1, respectively). Before and after PSM, patients in TTE group had lower 28-day all-cause mortality compared with patients in No-TTE group (10.76% vs 13.04%, χ2=13.535, P<0.001; 10.65% vs 18.80%, χ2=88.932, P<0.001), and Kaplan-Meier survival curves also revealed that patients in the TTE group had higher cumulative survival rate compared with patients in No-TTE group (Log-rank χ2=15.438, P<0.001; Log-rank χ2=75.360, P<0.001, respectively). Multivariate Cox regression analysis showed that TTE was an independent influencing factor for 28-day all-cause mortality before and after PSM ( HR=0.80, 95% CI 0.73-0.89, P<0.001; HR=0.58, 95% CI 0.51-0.65, P<0.001). And all subgroup analyses showed the similar results. Compared with patients in the No-TTE group, patients in the TTE group had higher volume of intravenous fluid on the first day and the second day after the diagnosis of AKI (both P<0.01). Patients in the TTE group had higher volume of urine output on the first day and the third day after the diagnosis of AKI (both P<0.01). The patients in the TTE group had a significantly lower duration of vasopressor-free and mechanical ventilation-free (both P<0.01). The usage of diuretic was significantly higher in the TTE group compared with that in the No-TTE group (54.1% vs 44.2%, χ2=65.609, P<0.001). With respect to serum creatinine, the reduction in serum creatinine within 48 hours after the diagnosis of AKI was higher in the TTE group than that in the No-TTE group [36.6(23.0, 97.2) μmol/L vs 30.1(14.2, 61.9) μmol/L, Z=-9.549, P<0.001]. Moreover, TTE group had shorter ICU stay than that in the No-TTE group [5.03(3.40, 8.90) d vs 5.37(3.77, 10.00) d, Z=-6.589, P<0.001]. There were no significant difference between the two groups in other secondary outcomes (all P>0.05). Conclusions:Timely TTE utilization after AKI incident is associated with better clinical outcomes for ICU patients.

Objective:To evaluate the safety and short-term outcomes of transfemoral transcatheter aortic valve replacement (TAVR) with domestic prostheses in patients with pure native aortic valve regurgitation (AR).Methods:A total of 16 patients with pure native AR who underwent transfemoral TAVR in the Renmin Hospital of Wuhan University from June 2019 to January 2022 were consecutively included in our study, and 24 patients with aortic stenosis (AS) who underwent transfemoral TAVR in the same period were selected as the control group. This study compared the baseline characteristics, baseline echocardiography, morphological characteristics of the aortic root, safety of the procedure and short-term outcomes between the two groups.Results:Compared with the AS group, the pure native AR group had a higher prevalence of baseline NYHA class Ⅲ or Ⅳ, a larger left ventricular end-diastolic diameter (LVEDD), a smaller relative ventricular wall thickness (RWT) (all P<0.05), a lower aortic root calcification score, and a larger sinus junction diameter, and cardiac angle (all P<0.05). During TAVR operation, the pure native AR group was treated with larger prostheses size, with a larger percentage in relation to the native annulus size and outflow tract (all P<0.05). There were 7 cases (43.8%) treated with 'valve in valve’, 2 cases (12.5%) with moderate paravalvular leak(PVL), and 2 cases (12.5%) with prostheses-migration to ascending aorta.However, no cases of death, transfer to surgery, coronary obstruction or annular rupture were observed in the pure native AR group. There were no statistical differences between the pure native AR group and AS group in device success rate (56.3% vs 62.5%, P>0.05) and 1-month all-cause mortality[0 (0/16) vs 4.2% (1/24), P>0.05]. The 6MWT, NT-proBNP, and NYHA were significantly improved at 1-month post TAVR compared with those before the procedure in the two groups (all P<0.05). Echocardiography showed significant reverse cardiac remodeling and improved left ventricular function compared with those before the procedure in the two groups. Conclusions:Transfemoral TAVR is a feasible and safe method for patients with pure native AR, and its short-term prognosis is similar to that in AS patients with well-established TAVR.

Objective:To establish the acute symptomatic osteoporotic thoracolumbar fracture (ASOTLF) classification system, and to examine the reliability and evaluate the effect of clinical application.Methods:A retrospective case series study was conducted to analyze the clinical data of 1 293 patients with osteoporotic thoracolumbar fracture(OTLF) admitted to Honghui Hospital from January 2016 to December 2018. There were 514 males and 779 females, aged 57-90 years [(71.4±6.3)years]. The T value of bone mass density was -5.0--2.5 SD [(-3.1±-0.4)SD]. According to the clinical symptoms a and fracture morphology, OTLF was divided into 4 types, namely type I(I occult fracture), type II(compressed fracture), type III (burst fracture) and type IV(unstable fracture). The type II was subdivided into three subtypes (type IIA, IIB, IIC), and the Type III into two subtypes (type IIIA, IIIB). of all patients, 75 patients (5.8%) were with type I, 500 (38.7%) with type II A, 134 (10.4%) with type IIB, 97 (7.5%) with type IIC, 442 (34.2%) with type IIIA, 27(2.1%) with type IIIB and 18 (1.4%) with type IV. After testing the validity of the classification, different treatment methods were utilized according to the classification, including percutaneous vertebroplasty (PVP) for Type I, PVP after postural reduction for Type II, percutaneous kyphoplasty (PKP) for Type IIIA, posterior reduction and decompression, bone graft fusion and bone cement-augmented screw fixation for Type IIIB, and posterior reduction, bone graft fusion and bone cement-augmented screw fixation for Type IV. The visual analog score (VAS), Oswestry disability index (ODI), Frankel grade of spinal cord injury, local Cobb Angle, and vertebral body angle (vertebral body angle) were recorded in all patients and in each type of patients before surgery, at 1 month after surgery and at the last follow-up. The neurological function recovery and complications were also recorded.Results:The patients were followed up for 24-43 months [(29.9±5.1)months]. A total of 3 000 assessments in two rounds were conducted by three observers. The overall κ value of inter-observer credibility was 0.83, and the overall κ value of intra-observer credibility was 0.88. The VAS and ODI of all patients were (5.8±0.7)points and 72.5±6.6 before surgery, (1.8±0.6)points and 25.0±6.3 at 1 month after surgery, and (1.5±0.6)points and 19.5±6.2 at the last follow-up, respectively (all P<0.05). The Cobb angle and vertebral body angle of all patients were (13.0±9.1)° and (8.0±4.6)° before surgery, (7.9±5.2)° and (4.6±2.9)° at 1 month after surgery, and (9.1±6.0)° and (5.8±3.0)° at the last follow-up, respectively (all P<0.05). At the last follow-up, VAS, ODI, Cobb Angle and VBA of each type of patients were significantly improved compared with those before surgery (all P<0.05). The spinal cord compression symptoms were found 1 patient with type IV and 5 patients with type IIIB preoperatively. At the last follow-up, neurological function improved from grade C to grade E in 1 patient and from grade D to grade E in 5 patients ( P<0.05). The lower limb radiation pain or numbness in 3 patients with type IV and 22 patients with type III preoperatively were fully recovered after surgical treatment at the last follow-up except for three patients. Conclusions:The ASOTLF classification is established and has high consistency and reliability. The classification-oriented treatment strategy has achieved a relatively satisfactory effect, indicating that the classification has a certain guiding significance for treatment of OTLF.

Objective:To investigate the predictive value of echocardiography hemodynamic parameters on 30-day survival rate after veno-arterial extracorporeal membrane oxygenation in refractory cardiogenic shock.Methods:A total of 44 patients with refractory cardiogenic shock who passed VA-ECMO weaning trial were retrospectively analyzed from September 2014 to February 2021. According to their 30-day survival outcomes after VA-ECMO removal, these patients were divided into the survival group (32 cases) and the death group (12 cases). Baseline data and the change rate of echocardiographic parameters between the first day of VA-ECMO and the day on VA-ECMO removal were compared, and the ultrasonic indicators affecting the survival of VA-ECMO within 30 days after withdrawal were determined.Results:The change rate of left ventricular ejection fraction(ΔLVEF%), the change rate of velocity time integral of the left ventricular outflow tract(ΔLVOT-VTI%), the change rate of ΔSa% and the change rate of right ventricular fractional area change(ΔRVFAC%) were improved significantly in the survival group ( P<0.05). The correlation coefficients between ΔLVEF% and ΔLVOT-VTI%, ΔLVEF% and ΔSa%, ΔLVEF % and ΔRVFAC% were 0.885, 0.861, 0.675, respectively( P<0.001); The correlation coefficient between ΔLVOT-VTI% and ΔSa was 0.918( P<0.001). ROC curve showed that the cut off values of ΔLVEF%, ΔLVOT-VTI%, ΔSa% and ΔRVFAC% to predict 30-day survival rate were 23.6%, 20.1%, 22.8% and 23.2% respectively, the sensitivity was 89.5%, 93%, 89.5% and 74.6% respectively, specificity was 66.7%, 66.7%, 66.8% and 75% respectively, the area under ROC curve (AUC) was 0.841, 0.867, 0.841 and 0.768, respectively. Conclusions:ΔLVEF%, ΔLVOT-VTI%, ΔSa% and ΔRVFAC% are predictive indicators of VA-ECMO withdrawl in patients with refractory cardiac shock. ΔLVOT-VTI% is the most valuable indicator of predicting 30-day survival rate after VA-ECMO withdrawl. Patients who meet two or more VA-ECMO echocardiographic indicators are more likely to succeed in VA-ECMO withdrawl. The improvement of right ventricular systolic function is a prerequisite for survival after 30 days of VA-ECMO withdrawal, while LVEF is an important criterion for survival after 30 days of VA-ECMO withdrawal.

Objective:To explore the feasibility of three-dimensional(3D) printing combined with mock circulatory system of flexible mitral valve model for hemodynamic testing in vitro based on ultrasound image data, making the transformation of 3D printing valve model from static to dynamic and from anatomical to functional, as well as assisting surgical plan for mitral valve diseases. Methods:A total of 10 subjects underwent three-dimensional transesophageal echocardiography (3D-TEE) and proved to be without mitral diseases were collected as mitral normal group from February 2017 to December 2018 in Renmin Hospital of Wuhan University, 10 mitral stenosis patients were collected as mitral stenosis group, and 10 mitral regurgitation patients were collected as mitral regurgitation group. Hemodynamic parameters of velocity (peak E), pressure gradient were obtained by two-dimensional transthoracic echocardiography in three groups, and the degree of mitral valve stenosis and regurgitation were also evaluated. Then 3D-TEE was performed to obtain the 3D volume image of mitral valve. After image post-processing and 3D modeling, the valve mold was printed with soluble material polyvinyl alcohol (PVA). The mixture of human skin silicone, silicone oil, starch and curing agent were poured into the mitral valve mold in a certain proportion to make flexible silicone mitral valve model. Then, the compliant valve model was placed in mock circulatory system (MCS), regularly opening and closing as it in vivo in the heart cycle. The hemodynamic parameters of mitral valve were measured again in vitro and the degree of stenosis and regurgitation was also evaluated respectively. Paired t test was used for statistical analysis of in vivo and in vitro measurements in two groups, and the consistency test was performed. Results:The mitral valve 3D-TEE images of all patients were successfully post-processed, mitral valve molds were printed and flexible models were made. In vitro hemodynamic tests were all completed. The opening and closing state of the valve model in vitro was similar to that in vivo. Mitral valve regurgitation was detected in mitral regurgitation group in vitro, with degree to that in vivo. There were no statistically significant differences in hemodynamic parameters measured in vivo and in vitro models (all P>0.05), with a high consistency ( r=0.76). Among the 10 patients with mitral stenosis and 10 patients with mitral regurgitation, 18 patients were evaluated as same degree as in vivo. Conclusions:3D printing of compliant mitral valve model based on ultrasound image is feasible, which reproduced hemodynamic features of mitral valve in vitro, setting foundation for further surgery simulation and clinical decision-making.