Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

Objective:To investigate the related factors affecting intraoperative blood loss in patients with spinal tumors undergoing preoperative selective arterial embolization.Methods:The clinical data of 90 patients with spinal tumors who underwent preoperative selective arterial embolization in the Affiliated Hospital of Jining Medical College and the Second Affiliated Hospital of Shanxi Medical University from January 2017 to December 2020 were retrospectively analyzed. The influencing factors of intraoperative bleeding were analyzed by using multiple linear regression.Results:There were statistically significant differences in intraoperative blood loss of spinal tumor patients undergoing preoperative selective arterial embolization with different blood supply abundance and the number of tumors involving vertebral body (all P < 0.05). There were no significant differences in age, gender, body mass index, interval after embolization, operation time, pathological type, tumor site, embolization degree, the number of embolized vessels, preoperative Frankel grade among different groups (all P > 0.05). Multiple linear regression analysis showed that the number of tumors involving vertebral body and tumor blood supply abundance were factors affecting intraoperative blood loss, and vertebra number and tumor blood supply were positively correlated with intraoperative blood loss (all P < 0.05). Conclusion:For patients with spinal tumors undergoing preoperative selective arterial embolization, the number of tumors involving vertebral body and the abundance of the tumor blood supply are factors affecting the amount of intraoperative bleeding.

OBJECTIVES: Cardiac hypertrophy and fibrosis are major pathological manifestations observed in left ventricular remodeling induced by angiotensin II (AngII). Low-intensity pulsed ultrasound (LIPUS) has been reported to ameliorate cardiac dysfunction and myocardial fibrosis in myocardial infarction (MI) through mechano-transduction and its downstream pathways. In this study, we aimed to investigate whether LIPUS could exert a protective effect by ameliorating AngII-induced cardiac hypertrophy and fibrosis and if so, to further elucidate the underlying molecular mechanisms. METHODS: We used AngII to mimic animal and cell culture models of cardiac hypertrophy and fibrosis. LIPUS irradiation was applied in vivo for 20 min every 2 d from one week before mini-pump implantation to four weeks after mini-pump implantation, and in vitro for 20 min on each of two occasions 6 h apart. Cardiac hypertrophy and fibrosis levels were then evaluated by echocardiographic, histopathological, and molecular biological methods. RESULTS: Our results showed that LIPUS could ameliorate left ventricular remodeling in vivo and cardiac fibrosis in vitro by reducing AngII-induced release of inflammatory cytokines, but the protective effects on cardiac hypertrophy were limited in vitro. Given that LIPUS increased the expression of caveolin-1 in response to mechanical stimulation, we inhibited caveolin-1 activity with pyrazolopyrimidine 2 (pp2) in vivo and in vitro. LIPUS-induced downregulation of inflammation was reversed and the anti-fibrotic effects of LIPUS were absent. CONCLUSIONS These results indicated that LIPUS could ameliorate AngII-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway, providing new insights for the development of novel therapeutic apparatus in clinical practice.

Objective: To explore the clinic-pathological significance of microRNA-145 expression in human cervical cancer and its ef-fects on Wnt/β-catenin signaling pathway. Methods: Real-time PCR was used to detect the expression of microRNA-145 in 62 cervical cancer samples. The correlation between microRNA-145 expression and the clinic-pathological parameters and its prognostic signifi-cance was analyzed. MicroRNA-145-expressing plasmid and non-sense plasmid were transfected into human cervical cancer HeLa cells, assigned into overexpressed microRNA-145 group and control group. Immunofluorescence staining was performed to detect the expression location of β-catenin. Top Flash luciferase reporter assay was performed to investigate the effects of microRNA-145 on the transcriptional activity of TCF/LEF and direct interactions with Cateninδ-1. Western blot was used to detect the effects of microRNA-145 on the expression of Cateninδ-1, C-MYC, and CyclinD1. Results: The patients with low microRNA-145 expression showed poorer prognosis [(41.28 ± 2.00) months vs . (46.06 ± 0.95) months, P<0.05]. β-catenin immunofluorescence was distributed within the cyto-plasm in the microRNA-145-overexpressed HeLa cells, but mainly within the nucleus and cytoplasm in the control cells. The luciferase reporter system indicated that the transcriptional activity of TCF/LEF was inhibited in the microRNA-145-overexpressed HeLa cells, and validated Cateninδ-1 was a target of miR-145. The expression of Cateninδ-1, C-MYC, and CyclinD1 was decreased in the microRNA-145-overexpressed HeLa cells. Conclusions: microRNA-145 may inhibit cervical cancer progression via Cateninδ-1 and inhibit the Wnt/β-catenin signaling pathway.

A limited number of microRNAs (miRNAs, miRs) have been reported to control postnatal cardiomyocyte proliferation, but their strong regulatory effects suggest a possible therapeutic approach to stimulate regenerative capacity in the diseased myocardium. This study aimed to investigate the miRNAs responsible for postnatal cardiomyocyte proliferation and their downstream targets. Here, we compared miRNA profiles in cardiomyocytes between postnatal day 0 (P0) and day 10 (P10) using miRNA arrays, and found that 21 miRNAs were upregulated at P10, whereas 11 were downregulated. Among them, miR-31a-5p was identified as being able to promote cardiomyocyte proliferation as determined by proliferating cell nuclear antigen (PCNA) expression, double immunofluorescent labeling for α-actinin and 5-ethynyl-2-deoxyuridine (EdU) or Ki-67, and cell number counting, whereas miR-31a-5p inhibition could reduce their levels. RhoBTB1 was identified as a target gene of miR-31a-5p, mediating the regulatory effect of miR-31a-5p in cardiomyocyte proliferation. Importantly, neonatal rats injected with a miR-31a-5p antagomir at day 0 for three consecutive days exhibited reduced expression of markers of cardiomyocyte proliferation including PCNA expression and double immunofluorescent labeling for α-actinin and EdU, Ki-67 or phospho-histone-H3. In conclusion, miR-31a-5p controls postnatal cardiomyocyte proliferation by targeting RhoBTB1, and increasing miR-31a-5p level might be a novel therapeutic strategy for enhancing cardiac reparative processes.
Animals ; Cell Count ; MicroRNAs ; Myocardium ; Myocytes, Cardiac* ; Negotiating ; Proliferating Cell Nuclear Antigen ; Rats

Objective: To evaluate the effect of transcatheter aortic valve replacement(TAVR) using Venus-A valve for treating patients with severe aortic stenosis. Methods: In this prospective study, 101 consecutive severe aortic stenosis patients with high surgical risk(Society of Thoracic Surgeon(STS) score ≥4%) or at prohibitive surgical risk were enrolled from 5 academic cardiovascular centers in China(Fuwai hospital, the second affiliated hospital of Zhejiang university school of medicine, West China hospital of Sichuan university, the first affiliated hospital of Nanjing medical university, Ruijin hospital of Shanghai Jiaotong university school of medicine) from September 2012 to January 2015, and Venus-A valves were used in TAVR for these patients. The primary endpoints were death from any cause and major stroke in 1 year. The secondary endpoints included efficacy and safety of TAVR in 1 year. Results: TAVR success rate was 97.9%(98/101), and 3 patients were transferred to receive surgical AVR. There were 85 patients using 1 Venus-A valve, and 13 patients underwent valve-in-valve implantation using 2 Venus-A valves. There were 1 case(1.0%) of stroke, 2 cases(2.0%)of acute myocardial infarction, 5 cases(5.0%) of pericardial effusion, 6 cases(5.9%) of severe vascular complication, and 2 cases(2.0%) of death after 7 days of TAVR. Meanwhile, aortic pressure gradient derived from echocardiography was significantly reduced when compared with pre-procedure level(11(8, 15) mmHg (1 mmHg=0.133 kPa) vs. 59(45, 71)mmHg, P<0.01), and there was no aortic root rupture or leaflets thrombosis. Rate of NYHA functional class ≤Ⅱ improvements were observed at 6 months follow-up when compared with pre-procedure(94.4%(84/89)vs. 21.3%(21/89), P<0.01). The primary endpoint was 7.9%(8/11), and the incidence of all cause death and stroke was 5.9%(6/101) and 2.0%(2/101) respectively at 1 year after the procedure. Kaplan-Meier survival analysis showed that cumulative survival rate was 94.1% at 1 year after the procedure. Conclusion TAVR using Venus-A valve for treating patients with severe aortic stenosis is effective and safe in the early and medium term post procedure.

Objective:To identify the novel HAND 1 mutation associated with congenital ventricular septal defect (VSD) and to perform the functional analysis.Methods:A total of 125 patients with congenital VSD and 210 control individuals were recruited,and their clinical data and blood samples were collected.The genomic DNA from each study subject was isolated,and all the coding exons of HAND1 were amplified.The amplicons from HAND 1 were sequenced to identify a sequence variation.The functional characteristics of the mutant HAND 1 were analyzed by a dual-luciferase reporter assay system.Results:A novel heterozygous HAND1 mutation c.355G＞T,equivalent to E119X,was identified in a patient with sporadic VSD.This nonsense mutation was absent in the 210 control subjects.Functional analysis revealed that the mutant HAND1 lost the ability to transactivate a target gene.Conclusion:A novel HAND1 mutation with VSD is identified in this study.

Objective To analyze the internal fixator remove time in different age patients after non-fusion cross injured vertebral screw of thoracolumbar vertebral fracture. Methods Sixty-eight patients who had underwent non-fusion cross injured vertebral screw were divided into 2 group according to the age:young group (20-44 years, 36 cases) and middle aged group (45-59 years, 32 cases). The numeric rating score (NRS), Oswestry disablility index (ODI), discoideum index (DI) and kyphotic Cobb angle 6, 9, 12 and 15 months after surgery were compared between 2 groups. Results The kyphotic Cobb angle, ODI and NRS 9, 12 and 15 months after surgery in 2 groups were significantly lower than those 6 months after surgery, which was in young group: (37.34 ± 6.86)° , (36.81 ± 6.78)° and (36.90 ± 6.97)° vs. (56.31 ± 3.56)° , (2.45 ± 0.55)%, (2.24 ± 0.53)% and (2.09 ± 0.41)% vs. (3.02 ± 0.89)%, (18.46 ± 2.73), (18.44 ± 3.05) and (18.28 ± 2.98) scores vs. (19.79 ± 2.85) scores, and in middle aged group: (37.11 ± 6.80)° , (35.58 ± 5.48)° and (35.40 ± 5.44)° vs. (56.03 ± 3.68)° , (2.21 ± 0.41)%, (2.08 ± 0.43)%and (1.97 ± 0.39)%vs. (3.04 ± 0.93)%, (19.17 ± 2.99), (18.57 ± 2.98) and (18. 43 ± 2.92) scores vs. (20.95 ± 2.49) scores. There were statistical differences (P<0.05). The DI 12 and 15 months after surgery in young group were significantly lower than that 6 and 9 months after surgery:(50.59 ± 4.60)%and (47.57 ± 4.30)%vs. (56.60 ± 3.98)%and (56.32 ± 3.87)%, and there were statistical differences (P<0.05). The DI 15 months after surgery in middle aged group was significantly lower than that 6, 9 and 12 months after surgery:(47.95 ± 4.87)%vs. (56.34 ± 3.97)%, (56.13 ± 3.88)%and (55.63 ± 3.94)%, and there were statistical differences (P<0.05). Conclusions The internal fixator remove time in the young patients after non-fusion of cross injured vertebral screw of thoracolumbar vertebral fracture is 9 months after surgery, and in the middle aged patients is 12 months after surgery. Intervertebral disc degeneration is one of the risk factors for delayed removal.

Objective To analyze the clinical effect of anterior cervical decompression with double-way connection intervertebral fusion device (ROI-C) implantation for type Ⅱ or type Ⅱ a Hangman fracture.Methods A retrospective study was made on 14 patients with type Ⅱ or type Ⅱ a Hangman fracture treated with anterior cervical ROI-C implantation between February 2011 and March 2014.The patients (11 males and 3 females) were aged between 22 and 46 years (mean,26.4 years).Nine patients sustained traffic injury,4 fall injury and 1 crash injury.Nine patients were classified as type Ⅱ and 5 type Ⅱ a according to the Levine-Edwards classification.All were completed cervical anteroposterior and lateral X-ray,CT scan,three-dimensional CT reconstruction and MRI examination after adnission.American Spinal Injury Association (ASIA) grade E was noted in all before operation.Clinical posttraumatic neck score,visual analogue scale (VAS) as well as angle deformity and displacement of the axis were recorded before operation and at the latest follow-up.Results All patients were operated successfully.Mean operation time was 61 min(range,45-116 min).There were no injuries of superior laryngeal nerve,hypoglossal nerve,throat wall and vessel during operation.Laryngeal edema,dysphagia,paralysis of tongue,hematoma and wound infection were not observed after operation.Mean period of follow-up was 24.2 months (range,4-32 months).All segments and fracture sites showed solid fusion after 3 months.No cages became subsided or displaced,no discs collapsed,and no malunion occurred at the latest follow-up.Data of preoperation and latest follow-up differed significantly with respect to clinical posttraumatic neck score[(53.1 ±7.2) points vs.(91.1 ±5.0)points],VAS[3.38(2.43,4.33)points vs.0.58(0,1.29) points],axis displacement[(4.0 ± 1.5) mm vs.(1.3 ± 1.2) mm],and angle deformityoftheaxis[(9.2±4.7)° vs.(2.1 ±1.9)°] (P＜O.05 or O.01).Conclusion Anterior cervical surgery with ROI-C implantation for type Ⅱ or type Ⅱa Hangman fracture provides good fusion rate and satisfactory clinical effect.