ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group （Saline） and hypertension group （Ang Ⅱ， which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps）， and supplemented daily with nicotinamide mononucleotide （300 mg/kg）， a precursor of NAD⁺. Blood pressure， endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA， SIRT3 and isocitrate dehydrogenase 2 （IDH2）. 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS， eNOS， SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure （P<0.001） and improved endothelial function and arterial stiffness （P<0.001） in hypertensive mice. In vitro， NMN improved endothelial function in AngII-stimulated endothelial cells （P<0.05） and attenuated mitochondrial oxidative stress levels （P<0.001）. Mechanistically， NMN elevated SIRT3 activity （P<0.001）， which subsequently enhanced IDH activity （P<0.001） and reduced oxidative stress levels in endothelial cells. Conversely， knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function （P<0.001）. ConclusionNAD⁺ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.

Objective To analyze the clinical features of chronic obstructive pulmonary disease (COPD) patients with heart failure (HF) in Nanjing and explore the influencing factors. Methods A total of 773 COPD inpatients were selected from January 2021 to January 2024 in Nanjing Combined Hospital of Traditional Chinese and Western Medicine, Nanjing Qixia District Hospital, Nanjing Lishui District People's Hospital, Nanjing Pukou District Hospital of Traditional Chinese Medicine and Nanjing First Hospital., and were divided into 2 groups according to the presence or absence of combined HF. The general data and medical records of the two groups were compared, the clinical characteristics of COPD patients with HF were summarized, and the influencing factors of COPD patients with HF were analyzed by multivariate logistic regression. Results Among the 242 patients (31.31%) with COPD had HF, chronic paroxysmal dyspnea was the most common first symptom, 169 patients (69.83%) had left heart failure, 63 patients (30.17%) were diagnosed as right heart failure or global heart failure , 17 patients (7.02%) had myocardial infarction. Multivariate logistic regression analysis showed that the risk of HF was 1.678 times and 1.691times higher in COPD groups ≥ 50 years old and male COPD groups than in < 50 years old and female groups, respectively; the risk of HF was 1.491 times higher in COPD groups engaged in physical work than in physical work groups; the risk of HF was 1.447 times and 1.580 times higher in COPD groups with hypertension and coronary heart disease than in COPD groups without hypertension and coronary heart disease, respectively; the risk of HF was 1.859 times higher in COPD groups smoking>400 vial/year than in COPD groups≤400 vial/ year; the risk of HF was 1.757 times higher in COPD groups with acute exacerbation frequency≥2 times/year than in COPD groups<2 times/year; the above differences were statistically significant (P<0.05). Conclusion Attention should be paid to elderly, male and heavy physical work group of COPD patients. Active treatment of hypertension and coronary heart disease, effective tobacco control and reduction of the frequency of acute exacerbation are effective ways to reduce the risk of HF in COPD patients in Nanjing.

convalescents, and to screen for broad-spectrum neutralizing antibodies against the SARS-CoV-2 RBD. Methods Using biotinylated RBD as a molecular probe, flow cytometry was employed to perform single-cell sorting of B cells from peripheral blood mononuclear cells (PBMCs) of convalescents. The obtained B cells were lysed and subjected to reverse transcription, followed by nested PCR amplification of the heavy and light chains of antibodies was conducted using random primers. The amplified products were cloned into corresponding expression vectors, and the respective matched heavy-light chain plasmids were co-transfected into 293F cells for expression. Monoclonal antibodies were then purified using Protein A column chromatography. Neutralization experiments were conducted with the wild-type (WT) pseudovirus, and antibodies with IC50<0.1 μg/mL were selected for further testing of neutralizing breadth and potency against the wild-type (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and currently prevalent pseudovirus strains (XBB, BA.5, BF.7). Results A total of 21 RBD-specific monoclonal B cells were obtained from two recovered patients, resulting in the isolation of 13 pairs of antibody light/heavy chains. Nine antibodies were successfully expressed, with P1-A1, P1-B6, and P1-B9 exhibiting IC50 values below 0.1 μg/mL against the pseudovirus of the wild-type strain (WT). Specifically, P1-B6 effectively neutralized the wild-type strain (WT), Beta variant (B.1.351), and Delta variant (B.1.617.2), with IC50 values reaching 0.01 μg/mL. P1-B9 demonstrated effective neutralization against the wild-type strain (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and Gamma variant (P.1) pseudoviruses, with IC50 values of 0.42 μg/mL, 0.63 μg/mL, 0.28 μg/mL, and 2.50 μg/mL, respectively. Additionally, P1-B6 exhibited good neutralization against BA.5 and BF.7 pseudoviruses, with IC50 values of 0.06 μg/mL and 0.09 μg/mL, respectively. Conclusions Infection with the SARS-CoV-2 WT strain can induce the generation of neutralizing antibodies with broad-spectrum activity. Generating these broadly neutralizing antibodies does not require an excessively high somatic hypermutation. The obtained antibodies can be used as candidates for SARS-CoV-2 diagnosis and prevention.

Objective:To investigate the effect and mechanism of isorhynchophylline (IRN) on angiotensin Ⅱ(Ang Ⅱ)-induced cardiac hypertrophy.Methods:H9c2 cells were co-cultured with Ang Ⅱ and different concentrations of IRN (0, 5, 10, 25, 50 μmol/L). The cell surface area and mRNA levels of cardiac hypertrophy markers atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) were detected to elucidate the effect of IRN on myocardial hypertrophy and the most effective concentration. H9c2 cells were co-cultured with Ang Ⅱ and IRN (25 μmol/L) at different times (0, 6, 12, 24 h) to elucidate the most effective time of inhibition. The phosphorylation levels of the signaling pathway were detected, and the effects of IRN and Akt inhibitor MK2206 on the phosphorylation levels of the signaling pathway were further explored to elucidate the underlying mechanisms.Results:Compared with the control group, the surface area of H9c2 cells, and the mRNA expression of myocardial hypertrophy markers ANP, BNP and β-MHC were significantly increased (all P<0.05). Pretreated with different concentrations of IRN (5, 10, 25, 50 μmol/L) could inhibit the increase in cell surface area induced by AngⅡ (all P<0.05), especially at the concentration of 25 μmol/ L ( P<0.01). IRN could time-dependently inhibit AngⅡ-induced activation of ANP, BNP, β-MHC mRNA (all P<0.05). AngⅡ caused increased phosphorylation levels of Akt, GSK3β, mTOR and FOXO3a. IRN could block AngⅡ-induced phosphorylation of the Akt signaling pathway. Conclusion:IRN attenuates AngⅡ-induced cardiomyocyte hypertrophy by inhibiting the Akt signaling pathway.

Objective:To analyze the coronary angiographic (CAG) characteristics of coronary artery lesion (CAL) in children with Kawasaki disease (KD), and to clarify the necessity of CAG in the diagnosis and treatment of KD combined with CAL in children.Methods:It was a retrospective study to analyze the clinical data, electrocardiogram, echocardiography, time and findings of CAG in children with KD and CAL who underwent CAG in Shanghai Children′s Medical Center of Shanghai Jiao Tong University School of Medicine from January 2013 to August 2022.The distribution, type, severity, and prognosis of CAL were analyzed.Results:A total of 117 children with KD and CAL were included in the analysis.The onset age of KD was from 2 months to 12.8 years old, and the age of performing CAG was from 8 months to 18.1 years old.A total of 234 coronary artery lesions were detected in 117 cases.Among them, CAL in the right coronary artery (RCA), left anterior descending branch (LAD), left main coronary artery and left circumflex artery were detected in 96 branches(41.1%), 78 branches(33.3%), 44 branches(18.8%), and 16 branches(6.8%), respectively.Unilateral coronary artery involvement was detected in 43 cases (36.8%), of which LAD was the dominant; while bilateral involvement was detected in 74 cases (63.2%), among which, LAD and RCA were the most involved arteries.Stratified by the degree of coronary involvement, large coronary aneurysms and severe coronary stenosis were most frequently occurred in the RCA and LAD.In contrast, 10 cases (13.6%), 20 cases (24.3%), 55 cases (45.8%) and 37 cases (67.3%) of intraluminal lesions were found in small, medium and large coronary aneurysms, and stenosis or occlusion, respectively.The incidence of intraluminal lesions tended to be higher in the site of severe lesions.CAG showed stenosis or occlusion in a total of 55 cases, and collateral circulation at varying degrees was found in cases of severe stenosis or occlusion.Conclusions:CAL in children with KD are complex and varied.Although clinical symptoms, routine electrocardiogram and cardiac ultrasound may indicate severe CAL.Their applications are limited by the diagnosis of the type (especially stenosis), degree, and extent of CAL, as well as the detection of extracoronary lesions.CAG is of great significance to identify vascular lesions and guide clinical management of KD combined with CAL in children.

Objective·To analyze the progression of children with severe coronary artery lesions due to Kawasaki disease by coronary artery angiography,and evaluate the diagnostic value of echocardiography in these children.Methods·A retrospective analysis was performed to enroll children with Kawasaki disease whose coronary artery lesions were graded Ⅳ or above from Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,from January 2013 to January 2023.The subjects were required to have received at least 2 times of coronary angiogram,and their clinical and imaging data were collected to analyze the progression of the lesions.Echocardiography results were compared with the results of the coronary angiogram.Results·A total of 21 children were included,including 15 males and 6 females,with a median age at onset of 3 years and 6 months,a median age at initial coronary angiography of 7 years and 11 months,a median interval of 4 years and 5 months between the time of onset and initial angiography,a median age at angiographic review of 9 years and 2 months,and a median interval of 1 year and 3 months between the time of initial angiography and review.Coronary stenosis or occlusion was detected in 13 children in the initial angiography,of whom 6 underwent coronary artery bypass grafting(CABG)and had their angiography reviews 1 year later.The review results showed that the bridging vessels were unobstructed and no obvious stenosis was observed.Fifteen children had progression of the lesions detected by echocardiography in the subsequent follow-up and had their angiogram reviews,of whom 8 had significant progression of the coronary lesions.Intracoronary balloon dilatation was performed in 1 case,and CABG was performed in another case.Sixteen lesions of coronary stenosis or occlusion were detected in the initial angiography in 21 children,while only 1 lesion of coronary stenosis was detected by echocardiography during the same period of time.Twenty-eight medium-to large-sized coronary aneurysms were detected in the initial angiography in the 21 children,and the diameters of the 28 aneurysms measured by echocardiography and coronary angiogram were subjected to the Bland-Altman analysis.The Bland-Altman analysis showed that the difference in maximum diameter between 2 methods was(1.63±2.33)mm,with 95％CI of-2.95-6.21 mm.Conclusion·Coronary artery lesions due to Kawasaki disease may be progressive;in the children with severe lesions,coronary artery stenosis or occlusion may be missed or misdiagnosed and some errors may exist in the measurement of diameters of aneurysms by echocardiography.Regular review of coronary angiography is needed.

Objective:To investigate the value of PET/CT imaging with 68Ga-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid-3 polyethylene glycol- D-Phe1-Tyr3-Thr8-octreotide Arg-Gly-Asp (NOTA-3P-TATE-RGD), a dual somatostatin receptor 2- and integrin α vβ 3- targeting tracer, in the evaluation of neuroendocrine neoplasms (NEN). Methods:From April 2021 to February 2022, 35 patients (19 males, 16 females; median age 54(41, 61) years) with histologically confirmed NEN in Peking Union Medical College Hospital were prospectively enrolled. All patients were scanned with both 68Ga-NOTA-3P-TATE-RGD and 68Ga-1, 4, 7, 1 0-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) PET/CT imaging within one week. The differences of the numbers of detected lesions, SUV max and tumor-to-background ratio (TBR) between the two imaging methods were compared by Wilcoxon signed-rank test. Results:Of the 35 patients, the total numbers of lesions detected by 68Ga-NOTA-3P-TATE-RGD and 68Ga-DOTATATE were 1 190 and 1 106, respectively. 68Ga-NOTA-3P-TATE-RGD and 68Ga-DOTATATE both detected 35 primary tumors and performed comparably in detecting lymph node metastases (4(1, 8) vs 4(1, 8); z=-0.45, P=0.655) and bone metastases (5(2, 60) vs 5(2, 66); z=-1.11, P=0.244). However, the number of liver lesions detected by 68Ga-NOTA-3P-TATE-RGD was significantly higher than that by 68Ga-DOTATATE (17(6, 27) vs 8(3, 26); z=-2.31, P=0.021). 68Ga-DOTATATE demonstrated higher SUV max than 68Ga-NOTA-3P-TATE-RGD (15.6(9.9, 24.9) vs 12.7(8.0, 18.4); z=-7.19, P<0.001), while the TBR of liver metastases was significantly lower (3.4(1.8, 5.5) vs 6.1(3.8, 10.8); z=-7.56, P<0.001). Conclusion:68Ga-NOTA-3P-TATE-RGD performs better than 68Ga-DOTATATE in the detection of liver metastases, while is comparable to 68Ga-DOTATATE in detecting lesions of other sites.

BACKGROUND: Meshes play a crucial role in hernia repair. However, the displacement of mesh inevitably leads to various associated complications. This process is difficult to be traced by conventional imaging means. The purpose of this study is to create a contrast-enhanced material with high-density property that can be detected by computed tomography (CT). METHODS: The contrast-enhanced monofilament was manufactured from barium sulfate nanoparticles and medical polypropylene (PP/Ba). To characterize the composite, stress tensile tests and scanning electron microscopy (SEM) was performed. Toxicity and biocompatibility of PP/Ba materials was verified by in vitro cellular assays. Meanwhile, the inflammatory response was tested by protein adsorption assay. In addition, an animal model was established to demonstrate the long-term radiographic effect of the composite material in vivo. Subsequent pathological tests confirmed its in vivo compatibility. RESULTS: The SEM revealed that the main component of the monofilament is carbon. In vitro cell experiments demonstrated that novel material does not affect cell activity and proliferation. Protein adsorption assays indicated that the contrast-enhanced material does not cause additional inflammatory responses. In addition, in vivo experiments illustrated that PP/Ba mesh can be detected by CT and has good in vivo compatibility. CONCLUSION These results highlight the excellent biocompatibility of the contrast-enhanced material, which is suitable for human abdominal wall tissue engineering.

Objective:To explore the efficacy and safety of sivelestat, a neutrophil elastase (NE) inhibitor, in the treatment of acute lung injury (ALI) in the intensive care unit (ICU).Methods:A retrospective analysis was performed on 171 patients with ALI in the ICU of the First Affiliated Hospital of Zhengzhou University from June 2020 to June 2021, including 77 patients in the sivelestat group and 94 patients in the conventional treatment group. Acute physiology and chronic health evaluation (APACHE) Ⅱ score, Murray lung injury score, oxygenation index (PaO 2/FiO 2 ratio), inflammatory cytokines (IL-6, IL-10, TNF-α), ventilator-free days (VFD), the length of ICU stay, and the 28-day mortality were collected to assess the efficacy of sivelestat. At the same time, adverse reactions and laboratory test results within 30 days after the use of sivelestat were recorded to assess the safety. Results:Compared with conventional treatment, oxygenation index, Murray lung injury scores, IL-6, IL-10, and TNF-α were significantly improved after 7 days of sivelestat treatment. Compared with the conventional treatment group, the VFD was significantly longer ( P = 0.0119) and the length of ICU stay was significantly shorter ( P = 0.0269) in the sivelestat group. The mortality was 14.29% in the sivelestat group and 22.34% in the conventional treatment group and, with no statistically significant. In the meantime, sivelestat did not increase adverse reactions within 30 days after treatment. Conclusions:Sivelestat treatment is safe and more effective than conventional treatment for ALI patients in the ICU.

Objective:To investigate the influence of low-dose ionizing radiation on the expression level of serum insulin-like growth factor binding protein-3 (IGFBP-3) in radiation workers in hospitals.Methods:183 radiation workers were randomly selected and grouped by work type including interventional radiology ( n=37), nuclear medicine ( n=43), radiotherapy ( n=48), and diagnostic radiology ( n=55). The content of IGFBP-3 in the serum of radiation workers was detected by ELISA assay. Results:It was observed that the expression level of serum IGFBP-3 in the four groups had significant differences ( F=6.056, P<0.05), and the content of serum IGFBP-3 in the interventional radiology group was significantly higher than that of nuclear medicine, radiotherapy, and diagnostic radiology groups ( t= 2.815, 3.611, 3.936, P<0.05). The concentration of IGFBP-3 in the serum of radiation workers among different annual effective dose groups was statistically different ( F=8.380, P<0.05), which gradually increased with the increase of annual effective dose and length of service ( rs=0.202, 0.151, P<0.05). Conclusions:The expression level of serum IGFBP-3 has the potential to be used as a biomarker to reflect the cumulative exposure of long-term chronic low-dose ionizing radiation.