[Impact of autologous hematopoietic stem cell transplantation on the efficacy of CAR-T treatment of relapsed/refractory multiple myeloma].

Objective: To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy. Methods: A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results: Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG (χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG (χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion: Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.

[HBeAg-positive patients hepatic tissue inflammatory activity and influencing factors during normal ALT and indeterminate phases].

Objective: To analyze the hepatic tissue inflammatory activity and influencing factors in HBeAg-positive patients during normal alanine aminotransferase (ALT) and indeterminate phases so as to provide a basis for evaluating the disease condition. Methods: Patients with HBeAg-positive with normal ALT and HBV DNA levels below 2 × 10(7) IU/ml from January 2017 to December 2021 were selected as the study subjects. A histopathologic liver test was performed on these patients. Age, gender, time of HBV infection, liver function, HBsAg level, HBV DNA load, genotype, portal vein inner diameter, splenic vein inner diameter, splenic thickness, and others of the patients were collected. Significant influencing factors of inflammation were analyzed in patients using logistic regression analysis, and its effectiveness was evaluated using receiver operating characteristic (ROC) curves. Results: Of the 178 cases, there were 0 cases of inflammation in G0, 52 cases in G1, 101 cases in G2, 24 cases in G3, and one case in G4. 126 cases (70.8%) had inflammatory activity ≥ G2. Infection time (Z=-7.138, P<0.001), γ-glutamyltransferase (t =-2.940, P=0.004), aspartate aminotransferase (t =-2.749, P=0.007), ALT (t =-2.153, P=0.033), HBV DNA level (t =-4.771, P=0.010) and portal vein inner diameter (t =-4.771, P<0.001) between the ≥G2 group and < G2 group were statistically significantly different. A logistic regression analysis showed that significant inflammation in liver tissue was independently correlated with infection time [odds ratio (OR)=1.437, 95% confidence interval (CI): 1.267-1.630; P<0.001)] and portal vein inner diameter (OR=2.738, 95% CI: 1.641, 4.570; P<0.001). The area under the curve (AUROC), specificity, and sensitivity for infection time and portal vein inner diameter were 0.84, 0.71, 0.87, 0.72, 0.40, and 0.95, respectively. Conclusion: A considerable proportion of HBeAg-positive patients have inflammation grade ≥G2 during normal ALT and indeterminate phases, pointing to the need for antiviral therapy. Additionally, inflammatory activity has a close association with the time of infection and portal vein inner diameter.

Proton Shell Gaps in N=28 Nuclei from the First Complete Spectroscopy Study with FRIB Decay Station Initiator.

The first complete measurement of the ß-decay strength distribution of _{17}^{45}Cl_{28} was performed at the Facility for Rare Isotope Beams (FRIB) with the FRIB Decay Station Initiator during the second FRIB experiment. The measurement involved the detection of neutrons and γ rays in two focal planes of the FRIB Decay Station Initiator in a single experiment for the first time. This enabled an analytical consistency in extracting the ß-decay strength distribution over the large range of excitation energies, including neutron unbound states. We observe a rapid increase in the ß-decay strength distribution above the neutron separation energy in _{18}^{45}Ar_{27}. This was interpreted to be caused by the transitioning of neutrons into protons excited across the Z=20 shell gap. The SDPF-MU interaction with reduced shell gap best reproduced the data. The measurement demonstrates a new approach that is sensitive to the proton shell gap in neutron rich nuclei according to SDPF-MU calculations.

[Progress and application of liver organoids in the study of liver cancer].

The incidence rate of liver cancer has been rising in recent years. Traditional cell line culture and human patient-derived tumor xenograft models, which are commonly used tools to simulate the occurrence of human liver cancer, have deepened the understanding of tumor occurrence, development, and drug resistance mechanisms. However, they cannot reflect the accurate state of cancer cells, the tumor microenvironment, or spatial structural characteristics. Recently, more in vitro-produced physiological liver organoids have been applied in the study of liver cancer. Liver organoid models have made breakthroughs in the occurrence and development mechanisms of liver cancer, personalized drug screening and biomarker identification, immunotherapy, and regenerative medicine applications. This paper mainly summarizes the progress and application of liver organoids processed in the study of liver cancer.

Holter electrocardiogram research trends and hotspots: bibliometrics and visual analysis.

OBJECTIVE: With the help of metrology, we can identify research hotspots and development trends in dynamic electrocardiography, and thereby provide corresponding reference material to aid further theoretical research. MATERIALS AND METHODS: All research data derived from the core collection of Web of Science, and all searches were completed on the same day (February 6, 2022). The obtained data were stored in plain text format and imported into CiteSpace for subsequent analysis. Citation analysis and visualization technology were used to draw a visual map of the research elements, using factors such as annual literature volume, country, journal, author, abstract, keywords, and citation. RESULTS: After screening, 2,937 papers were obtained. Research on ambulatory electrocardiography is increasing worldwide every year. Using research hotspots, keyword-clustering time-zone maps, and high-frequency emerging words, the research in this field was roughly divided into two stages, with 2017 as the divider. The first stage primarily focuses on areas such as atrial fibrillation, stroke, autonomic nerve function, catheter ablation, and T-wave alternation. The second stage saw the focus shift to wearable devices, sudden cardiac death, obstructive sleep apnea, feature extraction, cryptogenic stroke, and similar topics. CONCLUSIONS: With the development of various wearable technologies, the daily monitoring of healthy people engaged in sporting activities and the development of innovative analysis algorithms providing more accurate data may represent the hotspots and direction of future research.

[Three-dimensional volume rendering for dynamic characteristics of secundum atrial septal defect during various phases of the cardiac cycle and the impact on occluder selection].

Objective: To investigate the dynamic change of the secundum atrial septal defect (ASD) throughout the cardiac cycle, and assess its impact on occluder selection. Methods: This study retrospectively analyzed 35 patients with ASD who received electrocardiogram-gated coronary CT angiography (CCTA) throughout the cardiac cycle as well as interventional closure therapy in Fuwai Hospital from December 2016 to December 2019. The raw data were reconstructed into 20 phasic images of RR intervals (RRI) ranging from 0 to 95% in an increment of 5% and transmitted to a workstation for postprocessing. For each phase image, CT virtual endoscopy reconstruction technique (CTVE) was used to provide views of ASD. Axial sequence assisted CT volumetric measurement (CTAS) was used to calculate the maximum dimensions in axial planes (Da) and in superior-inferior direction (Db). Using a formula for converting circumference to diameter, the equivalent circle dimensions were calculated (De, De=minor axis+2 (major axis-minor axis)/3). Taking the data of 75% RRI phase, the patients were divided into Da75%RRI≥Db75%RRI group and Da75%RRIDa. Db is basically constant while Da changes significantly during cardiac cycle (10%-90% RRI). Nonetheless, both values peak and maintain the maximum status at end-systolic phase (35%-45% RRI). For patients with huge ASD, occluder selection should be based on the De at 35% RRI phase, which is helpful for the successful intervention.

[Rethinking about the treatment of polypoidal choroidal vasculopathy].

Polypoidal Choroidal Vasculopathy (PCV) is now categorized as a subtype of neovascular Age-related Macular Degeneration (nAMD), though the ocular manifestation and prognosis of PCV patients are quite distinct from nAMD. Due to its high prevalence in Asian population, retina specialists have implemented multiple randomized control trials (RCT) in recent years, aiming at providing grade 1 clinical evidence for current therapies and exploring efficient and affordable regimens for long-term management of PCV. Here we summarised current problems existed in available RCTs and prognostic biomarkers, and presented our thoughts based on previous clinical experiences which may be helpful for clinical management of PCV.

[Association of ambient fine particulate air pollution with hospitalization costs and stays for depression in China: a multicity analysis].

Objective: To explore the effect of fine particulate matter (PM2.5) pollution on depression hospitalization cost and length of stay in 57 cities of China. Methods: A total of 84 207 patients with depression in 57 cities of China from January 2013 to December 2017 were selected as the subjects. The demographic characteristics and hospitalization status of the patients were obtained from the database of basic medical insurance for urban workers and urban residents in China. The environmental exposure data of the same period were obtained from the national air quality real-time release platform of China Environmental Monitoring Station. A generalized additive model based on quasi-Poisson distribution was used to analyze PM2.5 exposure effect in each city, and the nonlinear mixing of moving average temperature, relative humidity and date was controlled by natural smooth spline function. Results: Among the included cities, southern cities accounted for 50.88% (29), and the number of female inpatients, hospitalization costs and hospitalization days accounted for 62.65%, 63.50% and 60.85% (42 735 cases, 567.78 million yuan and 1.14 million days, respectively). The proportion of hospitalized cases, hospitalization cost and length of stay in the age group of 40 to 64 years old were 59.15% (40 346 cases), 53.92% (482.15 million yuan) and 52.07% (0.98 million days), respectively. PM2.5 level was positively correlated with the number of hospitalized cases with depression, hospitalization cost and length of stay. When the 3-day moving average of PM2.5 exposure level increased by 10 µg/m3, the number of hospitalization cases increased by 0.64%. The attributed percentage (95%CI) of hospitalized cases, hospitalization costs and length of stay were 3.35% (0.57%-6.04%), 3.04% (0.52%-5.48%) and 3.07% (0.49%-5.56%), respectively. Subgroup analysis showed that the attributed percentage of hospitalization cases, hospitalization cost and length of stay to PM2.5 exposure ranged from 3.97% to 4.68%, 4.04% to 4.33% and 4.13% to 4.30% in northern China, male and cold season, respectively. Conclusion: PM2.5 exposure is associated with the increase of hospitalization cost and length of stay among Chinese urban population with depression.

[Experience and thoughts on digestive tract reconstruction after radical resection of adenocarcinoma of the esophagogastric junction].

In the surgical treatment of adenocarcinoma of the esophagogastric junction (AEG), the scope of lymph node dissection, surgical approach selection, extent of tumor resection and digestive tract reconstruction have always been controversial, with the digestive tract reconstruction in AEG facing many challenges especially. The digestive tract reconstruction is related to the extent of resection. At present, the digestive tract reconstruction after total gastrectomy includes Roux-en-Y anastomosis, jejunum interposition and its derivatives. According to different reconstruction methods, they can be divided into tube anastomosis, linear anastomosis and manual anastomosis. Anti-reflux digestive tract reconstruction after proximal gastrectomy mainly includes esophagogastric anastomosis, interposition jejunum and double channel anastomosis. At present, double channel anastomosis is the most common reconstruction method in China. Based on the concept of interposition tubular stomach and reconstruction of gastric angle for anti-reflux, we propose "Giraffe" anastomosis, which moves artificial fundus and His angle downward to retain more residual stomach, showing good gastric emptying and anti-reflux effect. In this paper, combined with our clinical experience and understanding, we discuss the selection and technical key points of digestive tract reconstruction methods in AEG, and suggest that composite anti-reflux mechanism design may be the development trend of anti-reflux reconstruction in the future. The composite mechanism includes the retention of gastric electrical pacemaker in greater curvature of the middle part of gastric body to increase the emptying capacity of residual stomach, the reconstruction of gastric fundus and His angle anti-reflux barrier, and the establishment of an interposition tubular stomach acting as a buffer zone in Giraffe construction, and so on.

[Functional outcomes of 100 patients with adenocarcinoma of the esophagogastric junction undergoing Cheng's GIRAFFE(®) reconstruction after proximal gastrectomy].

Objective: To investigate the functional outcomes and postoperative complications of Cheng's GIRAFFE reconstruction after proximal gastrectomy. Methods: A descriptive case series study was conducted. Clinical data of 100 patients with adenocarcinoma of the esophagogastric junction who underwent Cheng's GIRAFFE reconstruction after proximal gastrectomy in Cancer Hospital of University of Chinese Academy of Sciences (64 cases), Zhejiang Provincial Hospital of Chinese Medicine (24 cases), Lishui Central Hospital (10 cases), Huzhou Central Hospital (1 case) and Ningbo Lihuili Hospital (1 case) from September 2017 to June 2021 were retrospectively analyzed. Of 100 patients, 64 were males and 36 were females; the mean age was (61.3 ± 11.1) years and the BMI was (22.7±11.1) kg/m(2). For TNM stage, 68 patients were stage IA, 24 were stage IIA and 8 were stage IIB. Postoperative functional results and postoperative complications of radical gastrectomy with Giraffe reconstruction were analyzed and summarized. Gastroesophageal reflux disease questionnaire (RDQ) score and postoperative endoscopy were used to evaluate the occurrence of reflux esophagitis and its grade (grade N, grade A, grade B, grade C, and grade D from mild to severe reflux). The continuous data conforming to normal distribution were expressed as (mean ± standard deviation), and those with skewed distribution were presented as median (Q1, Q3). Results: All the 100 patients successfully completed R0 resection, including 77 patients undergoing laparoscopic surgery and 23 patients undergoing laparotomy. The Giraffe anastomosis time was (38.6±14.0) min; the blood loss was (73.0±18.4) ml; the postoperative hospital stay was 9.5 (8.2, 13.0) d; the hospitalization cost was (6.0±0.3) ten thousand yuan. Fourteen cases developed perioperative complications (14.0%), including 7 cases of pleural effusion or pneumonia, 3 cases of anastomotic leakage, 2 cases of gastric emptying disorder, 1 case of gastrointestinal hemorrhage and 1 case of anastomotic stenosis, who were all improved and discharged after symptomatic management. Patients were followed up for (33.3±1.6) months. Eight patients were found to have reflux symptoms by RDQ scale six months after surgery, and 11 patients (11/100,11.0%) were found to have reflux esophagitis by gastroscopy, including 6 in grade A, 3 in grade B, and 2 in grade C. All the patients could control their reflux symptoms with behavioral guidance or oral PPIs. Conclusion: Cheng's GIRAFFE reconstruction has good anti-reflux efficacy and gastric emptying function; it can be one of the choices of reconstruction methods after proximal gastrectomy.

[Impact of composite clinical worsening events on outcome of patients with pulmonary arterial hypertension associated with congenital heart disease].

Objective: To explore the impact of composite clinical worsening (cCW) events and its components on the prognosis of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH). Methods: This is a retrospective study. Patients who were diagnosed with CHD-PAH in Beijing Anzhen Hospital between January 2007 and July 2018, were included, and their baseline clinical data including demographic, clinical manifestations and New York Heart Association (NYHA) classification were collected retrospectively. All-cause deaths and clinical worsening events were recorded, which included syncope, PAH related hospitalization, NYHA classification deterioration and ≥ 2 PAH related clinical symptoms (dyspnea, hemoptysis, edema, chest pain, palpitations, cyanosis) appearance/progress. Three kinds of cCW events were defined: cCW1 (included PAH related hospitalization, NYHA classification deterioration), cCW2 (increased syncope on the basis of cCW1) and cCW3 (increased ≥ 2 PAH related clinical symptoms appearance/progress on the basis of cCW2). The Kaplan-Meier survival curve was used to analyze the long-term survival of the included patients. Univariate and multivariate Cox regression models were used to evaluate the impact of cCW events and their components on the risk of all-cause mortality. Results: A total of 525 patients with CHD-PAH were included in this study. The median age at diagnosis was 20.7 (11.2, 30.3) years. There were 43.8% children (<18 years), and 68.8% female patients. There were 431 patients (82.1%) with NYHA classification II. A total of 180 patients had PAH symptoms at diagnosis. The median follow-up time was 4.5 (2.6, 6.7) years. Forty-seven patients (9.0%) died during the follow-up period. Survival rates at 1, 5 and 10 years after diagnosis of PAH were 98.0%, 89.9% and 84.4%, respectively. Cox multivariate analysis showed that NYHA classification deterioration (HR=3.901, 95%CI 1.863-8.169, P<0.001), ≥2 PAH symptoms appearance/progress (HR=4.458, 95%CI 1.870-10.625, P<0.001), PAH-related hospitalization (HR=4.058, 95%CI 1.851-8.896, P<0.001) and syncope (HR=11.313, 95%CI 4.860-26.332, P<0.001) were independent predictors of increased risk of death. All 3 kinds of cCW events were significantly associated with the significantly increased risk of death, and cCW2 was highly predictive to increased risk of death (HR=15.476, 95%CI 4.346-37.576, P<0.001). Conclusions: The overall long-term prognosis of CHD-PAH patients in this study is relatively good. cCW events and its components (NYHA classification deterioration, ≥2 PAH symptoms occurrence/worsening, PAH-related hospitalization and syncope) have adverse influence on all-cause death in this patient cohort.

[Application of limiting antigen avidity enzyme immunoassay for estimating HIV-1 incidence in men who have sex with men].

Objective: To estimate the incidence of HIV-1 infection in men who have sex with men (MSM) in key areas of China through HIV-1 limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA), analyze the deviation from the actual results and identify influencing factors, and provided reference for improving the accuracy of estimation results. Methods: Based on the principle of the cohort randomized study design, 20 cities were selected in China based on population size and the number of HIV-positive MSM. The sample size was estimated to be 700 according to the HIV-1 infection rate in MSM. MSM mobile phone app. was used to establish a detection appointment and questionnaire system, and the baseline cross-sectional survey was conducted from April to November 2019. LAg-Avidity EIA was used to identify the recent infected samples. The incidence of HIV-1 infection was calculated and then adjusted based on the estimation formula designed by WHO. The influencing factors were identified by analyzing the sample collection and detection processes. Results: Among the 10 650 blood samples from the participants, 799 were HIV-positive in initial screening, in which 198 samples (24.78%) missed during confirmation test. Only 621 samples were received by the laboratory. After excluding misreported samples, 520 samples were qualified for testing. A total of 155 samples were eventually determined as recent infection through LAg-Avidity EIA; Based on the estimation formula , the incidence of HIV-1 infection in MSM in 20 cities was 4.06% (95%CI:3.27%-4.85%), it increased to 5.53% (95%CI: 4.45%-6.60%)after the adjusting for sample missing rate. When the sample missing rate and misreporting rate were both adjusted, the incidence of HIV-1 infection in the MSM increased to 5.66% (95%CI:4.67%-6.65%). The actual incidence of HIV-1 infection in MSM in the 20 cities might be between 4.06% and 5.66%. Conclusions: Sample missing and misreporting might cause the deviation of the estimation of HIV-1 infection incidence. It is important to ensure the sample source and the quality of sample collection and detection to reduce the deviation in the estimation of HIV-1 infection incidence.

Nuclear Charge Radii of the Nickel Isotopes

Collinear laser spectroscopy is performed on the nickel isotopes ^{58-68,70}Ni, using a time-resolved photon counting system. From the measured isotope shifts, nuclear charge radii R_{c} are extracted and compared to theoretical results. Three ab initio approaches all employ, among others, the chiral interaction NNLO_{sat}, which allows an assessment of their accuracy. We find agreement with experiment in differential radii δ⟨r_{c}^{2}⟩ for all employed ab initio methods and interactions, while the absolute radii are consistent with data only for NNLO_{sat}. Within nuclear density functional theory, the Skyrme functional SV-min matches experiment more closely than the Fayans functional Fy(Δr,HFB).

[Efficacy of 3D printed fistula stent in the treatment of enteroatmospheric fistula].

Objective: To investigate the efficacy of fistula stent made by 3D printing technique in the treatment of enteroatmospheric fistula. Methods: A descriptive case series study was carried out. INCLUSION CRITERIA: (1) patients with open abdomen; (2) patients with enteroatmospheric fistula. EXCLUSION CRITERIA: (1) patient with two or more fistulas; (2) distal obstruction; (3) bowel stenosis over 50%. According to above criteria, 17 EAF patients admitted to the General Surgery Department of Jinling Hospital from June 2019 to January 2020 were retrospectively included in study. Based on the intestinal radiography, CT reconstruction and finger exploration, the size of fistula, the diameter of the intestinal tube and the angle of the intestinal lumen around the fistula were assessed. The 3D printing fistula stent was designed and established based on estimated data, and then placed through the fistula. OUTCOME MEASUREMENTS: (1) success rate of stent implantation; (2) outflow of intestinal contents after implantation; (3) tolerated exercise time; (4) receiving definite operation time for intestinal fistula; (5) time to recovery of enteral nutrition. The t-test was used to compare the outflow amount of intestinal content before and after the stent implantation and the tolerated exercise time. The changes of the outflow amount of intestinal content and tolerated exercise time were analyzed by repeated measurement ANOVA. Results: Seventeen EAF patients with open abdomen included 13 males and 4 females. All the patients successfully received intestinal fistula stent implantation. Gastrointestinal angiography 2 days after implantation showed that the digestive tract was unobstructed, and the stent was successfully kept in place until definite surgery. No stent implantation-related adverse reactions were found in patients undergoing definite intestinal fistula surgery. The average outflow amount of intestinal fluid within 7 days after implantation decreased from (702.7±198.9) ml/d to on the first day after implantation (45.8±22.4) ml/d on the 7th day(F=10.380, P<0.001). The ambulatory time and exercise time of patients continued to increase after stent implantation. The average tolerated exercise time within 14 days after stent implantation increased from (9.1±3.8) min/d to (106.9±21.8) min/d (F=41.727, P<0.001). Within 120 days after stent implantation, 15 patients successfully underwent definite surgery for intestinal fistula and reconstruction of abdominal wall. Patients needed a median (IQR) of 3 (2, 5) days to recover enteral nutrition. The average time from stent placement to surgery was (87.2±17.6) days. Two patients died of severe abdominal infection with multiple organ failure. Conclusion: 3D printing fistula stent can significantly and the outflow of intestinal contents and the difficulty of nursing, and help to restore enteral nutrition and rehabilitation exercise as soon as possible in EAF patients with open abdomen.

[Establishment of mini-guts organoid and research on intestinal disease from the new perspective].

Intestinal organoids, also named "mini-guts", reconstitute sophisticated three-dimensional architecture recapitulating diversified intestinal epithelial cell types and physiology, which is driven by the proliferative and self-assembling characteristics of crypt stem cells. The initiation of organoids study relies on the identification of Lgr5+ crypt stem cells from different intestinal segments and the key role of EGF, Wnt, BMP/TGF-ß, Notch signal pathways within the microenvironment during the cultivation process. Besides constituting polarized crypt-villus structures, these "mini-guts" exhibit various effective functions of intestinal epithelium. Since 2009 when the culture system of small intestinal organoids was established by Sato et al, intestinal organoids excel conventional intestinal models depending on genetical mutation in multiple aspects and thus have become the hotspot among the research on intestinal diseases. Combined with genomics, material science and engineering, "mini-guts" have been widely applied to the research on intestinal development, intestinal transport physiology, epithelial barrier, pathogen-host interaction and the study on cystic fibrosis, infectious diarrhea, ulcerative colitis, Crohn's disease, intestinal cancer, etc. In this review, we summarize the new insights introduced by organoid into the research on intestinal diseases, and related research advances and applications.

[Safety and efficacy of transcatheter tricuspid valve replacement with LuX-Valve in patients with severe tricuspid regurgitation].

Objectives: To evaluate the safety and efficacy of LuX-Valve on the treatment of severe tricuspid regurgitation (TR). Methods: This is a prospective observational study. From September 2018 to March 2019, 12 patients with severe TR, who were not suitable for surgery, received LuX-Valve implantation in Changhai Hospital. LuX-Valve was implanted under general anesthesia and the guidance of transesophageal echocardiography and X-ray fluoroscopy. Access to the tricuspid valve was achieved via a minimally invasive thoracotomy and transatrial approach. Main endpoints were surgery success and device success. Surgery success was defined as successful implanting the device and withdrawing the delivery system, positioning the valve correctly and stably without severe or life-threatening adverse events. Device success was defined as satisfied valve function (TR severity reduction ≥ 2 grades, tricuspid gradient ≤ 6 mmHg (1 mmHg=0.133 kPa)), absence of malposition, valve failure and reintervention, major adverse events including device related mortality, embolization, conduction system disturbances and new onset shunt across ventricular septum at day 30 post implantation. Results: A total of 12 patients with severe to torrential TR were included in this study. The age was (68.5±6.9) years and 7 were female. All patients had typical right heart failure symptoms. Procedural success was achieved in all cases, there was no intraprocedural mortality or transfer to open surgery. TR significantly improved after LuX-Valve implantation (none/trivial in 8 patients, mild in 3 patients and moderate in 1 patient). The average device time was (9.2±4.2) minutes. Intensive care unit duration was 3.0 (2.0, 4.8) days. One patient died at postoperative day 18 due to non-surgery and device reasons. Transthoracic echocardiography at 30 days after operation showed that TR was significantly reduced (none/trivial in 8 patients, mild in 2 patients and moderate in 1 patient) and device success was achieved in 11 cases. All survived patients experienced a significant improvement in life quality with significantly improvement in New York Heart Association (NYHA) classification (Ⅰ and Ⅱ: 6/11 post operation vs. 0/11 before operation, P=0.012) and there were no device related complications in this patient cohort. Conclusions: LuX-Valve implantation is feasible, safe and effective for the treatment of patients with severe TR.

Myocardial motion-corrected phase-sensitive inversion recovery late gadolinium enhancement in free breathing paediatric patients: a comparison with single-shot coherent gradient echo ("TrueFISP") phase-sensitive inversion recovery.

AIM: To investigate the value of motion-corrected (MOCO) phase-sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) compared with single-shot balanced steady-state gradient echo ("TrueFISP", Siemens) PSIR in free breathing paediatric patients. MATERIALS AND METHODS: In this retrospective study, 238 paediatric patients underwent clinical contrast-enhanced cardiovascular magnetic resonance imaging (CMRI). Both the single-shot TrueFISP PSIR and MOCO PSIR sequences were performed on each child. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Two radiologists rated the quality of the images on a scale of 1-5 (1 = poor, 5 = very good). Bland-Altman, linear regression, and intraclass correlation coefficient were used to compared the extent of LGE of the single-shot TrueFISP PSIR and MOCO PSIR. Imaging artefacts were described and compared. RESULTS: Children ranged in age from 60 days to 17 years with an average age of 8.1 ± 3.8 years. MOCO PSIR had higher SNR and CNR than the single-shot TrueFISP PSIR (p<0.001). Mean quality ratings for short-axis imaging were 4 (interquartile range, 3-4) for single-shot TrueFISP PSIR and 4 (interquartile range, 4-5) for MOCO PSIR (p<0.001). The scan time was faster for single-shot TrueFISP PSIR than for MOCO PSIR. The myocardial LGE results were similar with high agreement between the single-shot TrueFISP PSIR and MOCO PSIR (ICC = 0.955-0.986). CONCLUSION: The MOCO PSIR sequence is feasible in children. MOCO PSIR is robust at high heart rates and can be performed without breath-holding with higher image-quality ratings than the single-shot TrueFISP PSIR.

[Clinical features and prognosis of low triiodothyronine syndrome in patients with acute myeloid leukemia].

Objective: To investigate the clinical features and prognosis of low triiodothyronine syndrome (LT3S) in patients with acute myeloid leukemia (AML) . Methods: A total of two 236 patients with AML who presented at the Jiangsu Provincial Hospital between January 2013 and December 2019 were included, and their data were retrospectively reviewed. The patients were divided into two groups, including the LT3S group and the non-LT3S group, according to their serum thyroxine level. The clinical characteristics and prognosis of the two groups were compared. Results: Among the 236 patients, 62 (26.3%) patients had LT3S. Serum-free T3 level was positively correlated with albumin (r=0.443, P<0.001) and hemoglobin (r=0.187, P=0.005) levels and negatively correlated with C-reactive protein (r=-0.406, P<0.001) and lactate dehydrogenase (r=-0.274, P<0.001) levels. The overall survival (OS) (7.5 months vs 29.9 months, P<0.001) and progression-free survival (PFS) (2.0 months vs 24.0 months, P<0.001) were significantly shortened in the LT3S group compared with the non-LT3S group. After propensity score matching, the OS (9.6 months vs 30.4 months, P=0.010) and PFS (3.0 months vs 30.0 months, P=0.014) were still significantly reduced in the LT3S group compared with the non-LT3S group. Therefore, LT3S was an independent risk factor for OS (HR=2.553, 95% CI 1.666-3.912, P<0.001) and PFS (HR=1.701, 95% CI 1.114-2.597, P=0.014) in patients with AML. Subgroup analysis suggested that patients with LT3S had a worse prognosis in patients with AML who were obese, fragile, or treated with standard chemotherapy. Conclusions: The occurrence of LT3S reflects the poor clinical status and prognosis of patients with AML.

METTL14 regulates M6A methylation-modified primary miR-19a to promote cardiovascular endothelial cell proliferation and invasion.

OBJECTIVE: Increasing evidence indicated that N6-methyl-adenosine (M6A) played a key role in a variety of pathophysiological processes. Methylases could promote the processing of mature mi-RNA in a M6A-dependent manner, thereby participating in the pathological cells' occurrence and development. However, the regulatory mechanism of M6A in atherosclerosis (AS) was still unclear. PATIENTS AND METHODS: Quantificational Real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of M6A, methyltransferase, demethylase transferase, miR-19a and other mi-RNA in atherosclerotic vascular endothelial cells (ASVEC). Cell Counting Kit (CCK8) was used to detect cell proliferation, the expression of PCNA was measured by Western Blot (WB) and qRT-PCR. Transwell assays were used to detect the invasion ability of ASVEC. Co-immunoprecipitation (Co-IP) was used to detect the binding of METTL14 to DGCR8. RNA Immunoprecipitation (RIP) was used to detect the binding of METTL14 to miR-19a. RESULTS: M6A modification levels and METTL14 methylation transferase were significantly overexpressed in ASVEC. Silencing METTL14 inhibited the proliferation and invasion of ASVEC. Low expression of METTL14 suppressed the binding of methylated RNA and RNA splicing related protein DGCR8. Moreover, silencing METTL14 significantly inhibited the expression of miR-19a while promoted the expression of primary pre-miR-19a. However, high expression of METTL14 obviously increased the expression of DGCR8 and methylated m6A. Furthermore, silencing miR-19a inhibited the proliferation and invasion of ASVEC. CONCLUSIONS: METTL14 increased the M6A modification of pri-miR-19a and promoted the processing of mature miR-19a, thus promoting the proliferation and invasion of ASVEC. These results suggested that METTL14/ M6A/ miR-19a signaling pathway may be a new target for atherosclerosis treatment.