Junyan Kan's research while affiliated with Nanjing Medical University and other places

Objective: To explore the long-term effects of intravascular ultrasound (IVUS) guidance on patients with acute coronary syndrome (ACS) undergoing drug-eluting stents (DES) implantation. Methods: Data used in this study derived from ULTIMATE trial, which was a prospective, multicenter, randomized study. A total of 1 448 all-comer patients were enrolled between 2014 August and 2017 May. Primary endpoint of this study was target vessel failure (TVF) at 3 years, including cardiac death, target-vessel-related myocardial infarction, and clinically-driven target vessel revascularization. Results: ACS was present in 1 136 (78.5%) patients, and 3-year clinical follow-up was available in 1 423 patients (98.3%). TVF in the ACS group was 9.6% (109/1 136), which was significantly higher than 4.5% (14/312) in the non-ACS group (log-rank P=0.005). There were 109 TVFs in the ACS patients, with 7.6% (43/569) TVFs in the IVUS group and 11.6% (66/567) TVFs in the angiography group (log-rank P=0.019). Moreover, patients with optimal IVUS guidance were associated with a lower risk of 3-year TVF compared to those with suboptimal IVUS results (5.4% (16/296) vs. 9.9% (27/273),log-rank P=0.041). Conclusions: This ULTIMATE-ACS subgroup analysis showed that ACS patients undergoing DES implantation were associated with a higher risk of 3-year TVF. More importantly, the risk of TVF could be significantly decreased through IVUS guidance in patients with ACS, especially in those who had an IVUS-defined optimal procedure.

The association between psoriasis and cardiovascular disease (CVD) has long been discussed and continually refined. However, there is currently a lack of prospective studies on the cardiovascular risk attributed to psoriasis in the United States general population. Representative adult participants were selected from the National Health and Nutrition Examination Survey (NHANES). Risks of cardiovascular symptoms and diseases prevalence were evaluated between participants with and without psoriasis. The hazards for all‐cause mortality and CVD mortality were stratified by psoriasis status. Mediation analysis was then conducted to identify potential mediators between psoriasis and cardiac death. Overall, 19 741 participants were included in the current study, 542 (2.7%) had psoriasis and 19 199 (97.3%) did not have psoriasis. After adjusting for known CVD risk factors, odds for hypertension (OR = 1.37, 95% CI: 1.13–1.66, p = 0.001), hypercholesterolemia (OR = 1.37, 95% CI: 1.13–1.64, p < 0.001) and angina pectoris (OR = 1.74, 95% CI: 1.11–2.60, p = 0.011) were higher in psoriasis patients. Compared with participants without psoriasis, moderate/severe but not mild patients showed significantly higher CVD mortality (HR = 2.55, 95% CI: 1.27–5.15, p = 0.009). This result was supported by subgroup analyses. Mediation analysis further suggested that the direct effect of moderate/severe psoriasis on CVD mortality accounted for 81.4% (65.8%–97.1%). Besides, the indirect effect might derive from disturbance of serum albumin, urea nitrogen and uric acid. Moderate‐to‐severe psoriasis is an independent risk factor for cardiovascular disease, making it necessary to regularly conduct cardiovascular disease‐related examinations for patients with higher severity of psoriasis in clinical settings.

Background The association between psoriasis and cardiovascular disease (CVD) has long been discussed and continually refined. However, there is currently a lack of prospective studies on the cardiovascular risk attributed to psoriasis in the general population. Methods Representative adult participants were selected from the National Health and Nutrition Examination Survey (NHANES). Risks of cardiovascular symptoms and diseases prevalence were evaluated between participants with and without psoriasis. The hazards for all-cause mortality and CVD mortality were stratified by psoriasis status. Mediation analysis was then conducted to identify potential mediators between psoriasis and cardiac death. Results Overall, 19,741 participants were included in the current study, 542 (2.7%) had psoriasis and 19,199 (97.3%) did not have psoriasis. After adjusting for known CVD risk factors, odds for hypertension (OR = 1.37, 95% CI: 1.13-1.66, p= 0.001), hypercholesterolemia (OR = 1.37, 95% CI: 1.13-1.64, p < 0.001) and angina pectoris (OR = 1.74, 95% CI: 1.11-2.60, p = 0.011) were higher in psoriasis patients. Compared with participants without psoriasis, moderate/severe but not mild patients showed significantly higher CVD mortality (HR = 2.55, 95% CI: 1.27-5.15, p = 0.009). This result was supported by subgroup analyses. Mediation analysis further suggested that the direct effect of moderate/severe psoriasis on CVD mortality accounted for 81.4% (65.8%-97.1%). Besides, the indirect effect might derive from disturbance of serum albumin, urea nitrogen and uric acid. Conclusions Moderate-to-severe psoriasis is an independent risk factor for cardiovascular disease, making it necessary to regularly conduct cardiovascular disease-related examinations for patients with higher severity of psoriasis in clinical settings.

Doxorubicin (Dox) is a powerful antineoplastic agent, but its usage is limited by the severe cardiotoxicity referred to as Dox-induced cardiomyopathy (DIC). However, the molecular mechanism underlying this cardiotoxicity is yet to be fully elucidated. Here, our current study sought to determine the role of ubiquitin-specific protease 36 (USP36), a nucleolar deubiquitinating enzyme (DUB), in the progress of DIC and its mechanism. We identified an increased expression of USP36 both in neonatal rat cardiomyocytes and H9C2 cells exposed to Dox, and USP36 silencing significantly ameliorated Dox-induced oxidative stress injury and apoptosis in vitro. Mechanistically, USP36 upregulation was observed to positively correlate with PARP1 expression, and its knockdown resulted in reduction of PARP1 levels. Further investigation showed that USP36 could bind to and mediate the deubiquitination of PARP1 and increase its protein stability in cardiomyocytes upon Dox exposure. Moreover, overexpression of wild-type (WT) USP36 plasmid, but not its catalytic-inactive mutant (C131A), stabilizes PARP1 in HEK293T cells. Herein, we also established DIC model in mice and observed a significant upregulation of USP36 in the heart. Cardiac knockdown of USP36 in mice by a type 9 recombinant adeno-associated virus (rAAV9)-shUSP36 significantly preserved cardiac function after Dox treatment and protected against Dox-induced in terms of structural changes within the myocardium. Collectively, these findings indicate that Dox promotes DIC progression by activating USP36-mediated PARP1 deubiquitination. This novel USP36/PARP1 axis may play an important regulatory mechanism in the pathogenesis of DIC.

GIMAPs are recognized as an important regulator in the carcinogenesis and development of lung cancer, but the function of GIMAP4 in the tumor microenvironment (TME) of lung cancers is unclear. In this study, we investigated the expression and variation of GIMAP4 in lung adenocarcinoma (LUAD), to explore its association with infiltration of immune cells. The Cancer Genome Atlas (TCGA) data and Gene Expression Omnibus (GEO) data were analyzed. Infiltration of immune cells was identified with TIMER (Tumor Immune Estimation Resource) and TISIDB (an integrated repository portal for tumor-immune system interactions). GIMAP4 expression declined in non-small-cell lung cancer (NSCLC), correlated with a poor overall survival (OS) in LUAD, indicating that GIMAP4 was a promising prognostic biomarker in LUAD. GIMAP4 mutation frequency was 1.76% in TCGA cohort and was relevant to the expression of immune components. TIMER and CIBERSORT analysis further confirmed that high GIMAP4 expression possibly promoted immune cell infiltration into the TME, with low GIMAP4 impairing the efficacy of immunotherapies targeting common immune check point inhibitors (ICI). GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses were performed to provide insights into biological processes involved in LUAD. GIMAP4 was expected to be a prognostic biomarker in LUAD and provides potential adjuvant or neoadjuvant therapeutic strategies for targeting ICIs.

Objective The optimal percutaneous coronary intervention (PCI) technique for bifurcation lesions remains controversial, especially considering the variability of the side branch (SB). A provisional stenting technique is currently recommended in most cases. This meta-analysis aimed to compare outcomes of different bifurcation PCI strategies, clarifying their scope of application. Methods Randomized controlled trials comparing PCI strategies for coronary bifurcation lesions were systematically retrieved from PubMed, Cochrane, Web of Science, and EBSCO literature databases without limitations on published date or language. Major adverse cardiovascular events (MACEs) were stipulated as main outcomes. Secondary outcomes of interest were all-cause mortality, cardiovascular mortality, target lesion revascularization (TLR), target vessel revascularization, myocardial infarction (MI), and stent thrombosis. Both pooled analysis and sub-group analysis were performed. Results Twenty-three randomized controlled trials with 6380 participants were included. Eighteen studies compared the provisional strategy with 2-stent approaches. No significant difference in MACEs (relative risk (RR), 1.16; 95% confidence interval (CI), 0.90–1.48; I2 = 62%) was found between 1-stent and 2-stent techniques. However, when SB lesion length was used as the separation condition, the 2-stent strategy was associated with fewer MACEs (RR, 1.87; 95% CI, 1.46–2.41; I2 = 70%), TLRs (RR, 2.13; 95% CI, 1.50–3.02; I2 = 59%), and MIs (RR, 2.17; 95% CI, 1.19–3.95; I2 = 52%) than the provisional strategy in those where SB lesions measured >10 mm long. Conclusions In the current work, there was no significant difference between 1-stent and 2-stent techniques in terms of MACEs or secondary outcomes. However, 2-stent approaches have clinical advantages over the provisional strategy in bifurcation when the SB lesion length is >10 mm due to fewer cases of TLR and MI.

Pulmonary arterial hypertension (PAH) is a devastating disorder characterized by excessive proliferation and vasoconstriction of small pulmonary artery vascular smooth muscle cells (PASMCs). Coptidis rhizoma (CR) because of the complexity of the components, the underlying pharmacological role and mechanism of it on PAH remains unknown. In this article, the network pharmacological analysis was used to screen the main active constituents of CR and the molecular targets that these constituents act on. Then, we evaluated the importance of berberine and quercetin (biologically active components of CR) on the proliferation and migration of PASMCs and vascular remodeling in experimental models of PAH. Our results showed that berberine and quercetin effectively inhibited the proliferation and migration of hypoxia-induced PASMCs in a manner likely to be mediated by the suppression of MAPK1, NADPH oxidase 4 (NOX4), and cytochrome P450 1B1 (CYP1B1) expression. Furthermore, berberine and quercetin treatment attenuates pulmonary hypertension, reduces right ventricular hypertrophy, and improves pulmonary artery remodeling in monocrotaline-induced pulmonary hypertension in rat models. In conclusion, this research demonstrates CR might be a promising treatment option for PAH, and the network pharmacology approach can be an effective tool to reveal the potential mechanisms of Chinese herbal medicine.

Objective: To explore the long-term effect of intravascular ultrasound (IVUS) guidance on patients with chronic kidney disease (CKD) undergoing drug-eluting stent (DES) implantation. Methods: Data used in this study derived from ULTIMATE trial, which was a prospective, multicenter, randomized study. From August 2014 to May 2017, 1 448 patients with coronary heart disease undergoing DES implantation were selected from 8 domestic centers and randomly divided into two groups in the ratio of 1∶1 (IVUS or coronary angiography guided stent implantation). A total of 1 443 patients with the baseline serum creatine available were enrolled. The patients were divided into CKD group and non CKD group. CKD was defined as the estimated glomerular filtration rate (eGFR) derived from Cockcroft Gault (CG) formula< 60 ml·min-1·1.73 m-2 for at least 3 months. Primary endpoint of this study was target vessel failure (TVF) at 3 years, including cardiac death, target vessel myocardial infarction, and clinically-driven target vessel revascularization. Kaplan Meier method was used for survival analysis, and log rank test was used to compare the occurrence of end-point events in each group. Cox proportional hazards model was used to calculate HR and 95%CI, and interaction was tested. Multivariate Cox regression was used to analyze the independent influencing factors of TVF. Results: A total of 1 443 patients with coronary heart disease were enrolled in this study, including 349 (24.2%) patients in CKD group and 1 094 patients in non CKD group. In CKD group, IVUS was used to guide stent implantation in 180 cases and angiography was used in 169 cases; in non CKD group, IVUS was used to guide stent implantation in 543 cases and angiography was used in 551 cases. Three-year clinical follow-up was available in 1 418 patients (98.3%). The incidence of TVF in CKD group was 12.0% (42/349), which was higher than that in non CKD group (7.4% (81/1 094) (P = 0.01). The difference was mainly due to the higher cardiac mortality in CKD group (4.6% (16/349) vs. 1.5% (16/1094), P<0.001). In CKD group, the incidence of TVF in patients who underwent IVUS guided stent implantation was lower than that in angiography guided stent implantation (8.3% (15/180) vs. 16.0% (27/169), P = 0.03). There was no significant difference in the incidence of TVF between IVUS guided stent implantation and angiography guided stent implantation in non CKD group (5.9% (32/543) vs. 8.9% (49/551), P = 0.06), and there was no interaction (P = 0.47). Multivariate Cox regression analysis showed that IVUS guidance (HR = 0.56, 95%CI 0.39-0.81, P = 0.002), CKD (HR = 1.83, 95%CI 1.17-2.87, P = 0.010) and stent length (every 10 mm increase) (HR = 1.11, 95%CI 1.04-1.19, P = 0.002) were independent risk factors for TVF within 3 years after DES implantation. Conclusions: CKD patients undergoing DES implantation are associated with a higher risk of 3-year TVF. More importantly, the risk of TVF could be significantly decreased through IVUS guidance in comparison with angiography guidance in patients with CKD.