Imidazo[1,2-b]pyridazines as inhibitors of DYRK kinases.

Selective inhibitors of DYRK1A are of interest for the treatment of cancer, Type 2 diabetes and neurological disorders. Optimization of imidazo [1,2-b]pyridazine fragment 1 through structure-activity relationship exploration and in silico drug design efforts led to the discovery of compound 17 as a potent cellular inhibitor of DYRK1A with selectivity over much of the kinome. The binding mode of compound 17 was elucidated with X-ray crystallography, facilitating the rational design of compound 29, an imidazo [1,2-b]pyridazine with improved kinase selectivity with respect to closely related CLK kinases.

Induction of breast cancer cell apoptosis by novel thiouracil-fused heterocyclic compounds through boosting of Bax/Bcl-2 ratio and DFT study.

Breast cancer is a common public health disease causing mortality worldwide. Thus, providing novel chemotherapies that tackle breast cancer is of great interest. In this investigation, novel pyrido[2,3-d]pyrimidine derivatives 3,4,(6a-c),(8a,b),9-20 were synthesized and characterized using a variety of spectrum analyses. The geometric and thermal parameters of the novel thiouracil derivatives 3,4,6a,(8a,b),11,12,17,18, 19 were measured using density functional theory (DFT) via DFT/B3LYP/6-31 + G(d,p) basis set. All synthesized compounds were evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) method using MCF-7 and MDA-MB-231 breast cancerous cells, compound 17 had the maximum anticancer activity against both breast cancerous cells, recording the lowest half-maximal inhibitory concentration (IC50) values (56.712 µg/mL for MCF-7 cells and 48.743 µg/mL for MDA-MB-231 cells). The results were confirmed in terms of the intrinsic mechanism of apoptosis, where compound 17 had the highest percentage in the case of both cancer cells and recorded Bax (Bcl-2 associated X)/Bcl-2 (B-cell lymphoma 2) ratio 17.5 and 96.667 for MCF-7 and MDA-MB-231 cells, while compound 19 came after 17 in the ability for induction of apoptosis, where the Bax/Bcl-2 ratio was 15.789 and 44.273 for both cancerous cells, respectively. Also, compound 11 recorded a high Bax/Bcl-2 ratio for both cells. The safety of the synthesized compounds was applied on normal WI-38 cells, showing minimum cytotoxic effect with undetectable IC50. Compounds 17, 11, and 19 recorded a significant increase of p53 upregulated modulator of apoptosis (PUMA) expression levels in the cancerous cells. The DFT method was also used to establish a connection between the experimentally determined values of the present investigated compounds and their predicted quantum chemical parameters. It was concluded that Compounds 17, 11, and 19 had anti-breast cancer potential through the induction of apoptotic Bax/Bcl-2 and PUMA expression levels.

Discovery of a stilbenoid-flavanone hybrid as an antitumor Wnt/ß-catenin signaling pathway inhibitor.

A series of designed stilbenoid-flavanone hybrids featuring sp3-hybridized C2 and C3 atoms of C-ring was evaluated against colorectal cancers presented compounds 4, 17, and 20 as the most potential compounds among explored compounds. Evaluation of the anticancer activity spectrum of compounds 4, 17, and 20 against diverse solid tumors presented compounds 17 and 20 with interesting anticancer spectrum. The potencies of compounds 17 and 20 were assessed in comparison with FDA-approved anticancer drugs. Compound 17 was the, in general, the most potent showing low micromolar GI50 values that were more potent than the standard FDA-approved drugs against several solid tumors including colon, brain, skin, renal, prostate and breast tumors. Compound 17 was subjected for evaluation against normal cell lines and was subjected to a mechanism study in HCT116 colon cancer cells which presented it as an inhibitor of Wnt signaling pathway triggering G2/M cell cycle arrest though activation of p53-p21 pathway as well as intrinsic and extrinsic apoptotic death of colon cancer cells. Compound 17 might be a candidate for further development against diverse solid tumors including colon cancer.

Microvascular changes following exposure to iodinated contrast media in vitro. A qualitative comparison to serum creatinine concentrations in post-cardiac catheterization patients.

INTRODUCTION: Contrast-associated acute kidney injury (CA-AKI) is characterized as a loss of renal function following radiological contrast media administration. While all contrast media induce variable changes in microvascular endothelial cells in vitro, only few studies report clinical significance of their findings. A comprehensive assessment of the effect of iodinated contrast media on the renal function in vitro and in vivo is essential. The aim of our study was to morphometrically quantify the effect of two different contrast media (Iobitridol and Iodixanol) on vascular endothelial capillaries in vitro and to analyze their effect on the renal function of patients who underwent cardiac catheterization including the intra-arterial administration of contrast media, by measuring serum creatinine concentration (SCr), a byproduct of muscle metabolism, primarily excreted by the kidneys. Our hypothesis suggests that conducting a qualitative comparison of both outcomes will enable identification of differences and similarities between in vitro and in vivo exposure. MATERIAL AND METHODS: In vitro, co-cultures of human dermal fibroblasts and human dermal microvascular endothelial cells forming capillary beds were exposed to a mixture of phosphate buffered saline and either Iobitridol, Iodixanol, or one of their supplements EDTA or Trometamol for 1.5 or 5 min. Negative control co-cultures were exposed exclusively to phosphate buffered saline. Co-cultures were either directly fixed or underwent a regeneration time of 1, 3 or 7 days. An artificial intelligence software was trained for detection of labeled endothelial capillaries (CD31) on light microscope images and measurements of morphometric parameters. In vivo, we retrospectively analyzed data from patients who underwent intra-arterial administration of contrast media and for whom SCr values were available pre- and post-contrast exposition (1, 3, and 7 days following procedure). Temporal development of SCr and incidence of CA-AKI were assessed. Both exposure types were qualitatively compared. RESULTS: In vitro, Iobitridol, Iodixanol and EDTA induced a strong decrease of two morphometric parameters after 3 days of regeneration. In vivo, a significant increase of SCr and incidence of CA-AKI was observed 3 days following procedure in the post-contrast media patients. No difference was observed between groups. DISCUSSION: Two of the morphometric parameters were inversely proportional to the SCr of the patients. If the endothelial damages observed in vitro occur in vivo, it may result in renal hypoxia, inducing a loss of kidney function clinically translated into an increase of SCr. Further development of our in vitro model could allow closer replication of the internal structure of a kidney and bridge the gap between in vitro studies and their clinical findings.

Structure-Based Drug Design for Targeting IRE1: An in Silico Approach for Treatment of Cancer.

BACKGROUND: Endoplasmic Reticulum (ER) stress and Unfolded Protein Response (UPR) play a key role in cancer progression. The aggregation of incorrectly folded proteins in the ER generates ER stress, which in turn activates the UPR as an adaptive mechanism to fix ER proteostasis. Inositol-requiring enzyme 1 (IRE1) is the most evolutionary conserved ER stress sensor, which plays a pro-tumoral role in various cancers. Targeting its' active sites is one of the most practical approaches for the treatment of cancers. OBJECTIVE: In this study, we aimed to use the structure of 4µ8C as a template to produce newly designed compounds as IRE1 inhibitors. METHODS: Various functional groups were added to the 4µ8C, and their binding affinity to the target sites was assessed by conducting a covalent molecular docking study. The potential of the designed compound for further in vitro and in vivo studies was evaluated using ADMET analysis. RESULTS: Based on the obtained results, the addition of hydroxyl groups to 4µ8C enhanced the binding affinity of the designed compound to the target efficiently. Compound 17, which was constructed by the addition of one hydroxyl group to the structure of 4µ8C, can construct a strong covalent bond with Lys907. The outcomes of ADMET analysis indicated that compound 17 could be considered a drug-like molecule. CONCLUSION: Our results revealed that designed compound 17 could inhibit IRE1 activity. Therefore, this designed compound is a remarkable inhibitor of IRE1 and introduces a promising therapeutic strategy for cancer treatment.

Design, synthesis, and structure-activity relationship of novel RIPK2 inhibitors.

The NOD1/2 (nucleotide-binding oligomerization domain-containing protein 1/2) signaling pathways are involved in innate immune control and host defense. NOD dysfunction can result in a variety of autoimmune disorders. NOD-induced generation of inflammatory cytokines is mediated by receptor-interacting protein kinase 2 (RIPK2), which has been considered as a promising therapeutic target. Herein, we disclose the design, synthesis, and SAR study of a series of RIPK2 inhibitors. The lead compound 17 displayed a high affinity for RIPK2 (Kd = 5.9 nM) and was capable of inhibiting RIPK2 kinase function in an ADP-Glo assay. In vitro DMPK studies showed that compound 17 had good metabolic stability and no CYP inhibition. Compound 17 effectively suppressed inflammatory cytokine production in both cells and animal model.

Degradation of iopromide during the UV-LED/chlorine reaction: Effect of wavelength, radical contribution, transformation products, and toxicity.

Three different UV-LED wavelengths (265, 310, and 365 nm) were used in the UV-LED/chlorine reaction to investigate the degradation mechanism of iopromide (IPM) at different wavelengths, a representative iodinated contrast media compound. The degradation rate (k'IPM) increased from pH 6-8 at 265 nm, but, decreased as the pH increased up to 9 at 310 nm and 365 nm. Radical scavenging experiments showed that reactive chlorine species (RCS) are the dominant radical species at all wavelengths, but a higher contribution of OH• was observed at lower pH and longer wavelengths. The contribution of RCS decreased but the contribution of OH• increased as the wavelength increased. Among RCS, the largest contribution was found to be ClO•. Total nine transformation products (TPs) were identified by LC-QTOF-MS during the UV-LED/chlorine reaction at 265 nm. Based on the identified TPs and their time profiles, we proposed a degradation pathway of IPM during UV-LED/chlorine reaction. The Microtox test using V. fischeri showed that no significant increase in toxicity was observed at all wavelengths. The synergistic effect of UV-LED and chlorine was greater at a higher wavelength by the electrical efficiency per order (EEO) calculation.

Iopromide and Iodixanol in the Development of Postoperative Contrast Nephropathy in Patients with Renal Insufficiency: A Meta-Analysis.

In order to compare the effects of iopromide and isoxazole on postoperative contrast-induced nephropathy in patients with renal insufficiency, the paper searches for randomized controlled trials and retrospective cohort studies comparing the effects of iopromide and iodixanol on renal function in patients with renal insufficiency after surgery. The data are extracted from eligible studies. We tried to assess the incidence of contrast-agent nephropathy, preoperative and postoperative serum creatinine indicators, and mortality. This paper includes 8 studies with a total of 1243 patients. The incidence of contrast-induced nephropathy in the iopromide group is higher than that in the iodixanol group, and there is no significant difference between the two groups in postoperative mortality and preoperative serum creatinine expression. Sensitivity analysis and funnel chart show that our research is robust and has low publication bias. Our research shows that in patients with renal insufficiency, the incidence of contrast-medium nephropathy in the iopromide group is higher than that in the iodixanol group. Iodixanol is safer and has less effect on patients' serum creatinine levels.

Risk of Hypersensitivity Reactions to Iopromide in Children and Elderly: An Analysis of 132,850 Patients From 4 Observational Studies and Pharmacovigilance Covering >288 Million Administrations.

PURPOSE: The aim of this study was to analyze the risk of hypersensitivity reactions (HSRs) to iopromide in children and elderly patients in comparison to adults. MATERIALS AND METHODS: Four observational studies were pooled and analyzed (analysis I). In addition, spontaneous reports from 1985 to 2020 from the pharmacovigilance database were evaluated (analysis II). All patients received iopromide for angiographic procedures or contrast-enhanced computed tomography in various indications. In analysis I, a nested case-control analysis, including a multivariable logistic regression model, based on pooled observational study data, was performed. Cases were defined as patients with a typical and unequivocal HSR; controls were patients without any recorded reaction. In analysis II, all spontaneous reports on HSRs after iopromide administration recorded in the pharmacovigilance database were descriptively analyzed. Exposure estimates on the size of the exposed age groups were derived from sales data and data from market research. The primary target variable was the risk of HSR to iopromide in children (<18 years) and elderly patients (≥65 years) compared with adults (≥18 to <65 years). RESULTS: In analysis I, a total of 132,850 patients were included (2978 children, 43,209 elderly, and 86,663 adults). Hypersensitivity reactions were significantly less frequent in children (0.47%) and elderly (0.38%) compared with adults (0.74%). The adjusted odds ratio (vs adults) for children was 0.58 (95% confidence interval, 0.34-0.98; P < 0.043), and that for the elderly was 0.51 (95% confidence interval, 0.43-0.61; P < 0.001), indicating a lower risk for both subpopulations as compared with adults. In analysis II, of the overall >288 million iopromide administrations, 5.87, 114.18, and 167.97 million administrations were administered to children, elderly, and adults, respectively. The reporting rate for HSRs in children (0.0114%) and elderly (0.0071%) was significantly lower as compared with adults (0.0143%) (P < 0.0001). CONCLUSIONS: Hypersensitivity reactions to iopromide were significantly less frequent in children and elderly compared with adults.

Calorie Restriction Protects against Contrast-Induced Nephropathy via SIRT1/GPX4 Activation.

Calorie restriction (CR) extends lifespan and increases resistance to multiple forms of stress, including renal ischemia-reperfusion (I/R) injury. However, whether CR has protective effects on contrast-induced nephropathy (CIN) remains to be determined. In this study, we evaluated the therapeutic effects of CR on CIN and investigated the potential mechanisms. CIN was induced by the intravenous injection of iodinated contrast medium (CM) iopromide (1.8 g/kg) into Sprague Dawley rats with normal food intake or 40% reduced food intake, 4 weeks prior to iopromide administration. We found that CR was protective of CIN, assessed by renal structure and function. CM increased apoptosis, reactive oxygen species (ROS), and inflammation in the renal outer medulla, which were decreased by CR. The silent information regulator 1 (SIRT1) participated in the protective effect of CR on CIN, by upregulating glutathione peroxidase 4 (GPX4), a regulator of ferroptosis, because this protective effect was reversed by EX527, a specific SIRT1 antagonist. Our study showed that CR protected CIN via SIRT1/GPX4 activation. CR may be used to mitigate CIN.

High Concentration of Iopromide Induces Apoptosis and Autophagy in Human Embryonic Kidney Cells via Activating a ROS-dependent Cellular Stress Pathway.

BACKGROUND/AIM: The use of iodinated contrast media may impair renal function. However, no report has addressed the nephrotoxicity of high doses of iodinated contrast media in normal kidney cells and its associated molecular mechanisms. MATERIALS AND METHODS: Cell proliferation was assessed using the MTT assay. Cell death was evaluated through examining the morphological changes and TUNEL assay. Autophagy was detected through acridine orange staining and lysotracker staining. Reactive oxygen species production and AKT kinase activity were examined. RESULTS: Iopromide induced cell death and triggered apoptosis and autophagy in HEK 293 cells. Cell viability was significantly restored in the presence of a pan-caspase inhibitor or a ROS scavenger, N-acetyl-L-cysteine. AKT kinase activity was found to be reduced in iopromide-treated HEK 293 cells. CONCLUSION: High concentrations of iopromide induce cell damage, apoptosis, and autophagy through down-regulating AKT and ROS-activated cellular stress pathways in HEK 293 cells.

[Iopromide-Induced Encephalopathy: A Case Report and Literature Review].

A 42-year-old male was admitted for paroxysmal syncope for 10 + months, chest tightness for 20 + days and chest pain for 10 + days. The patient was diagnosed with hypertrophic cardiomyopathy. The patient did not have a history of hypertension or diabetes. Coronary angiography and left ventricular cardiac catheterization were done in order to examine the coronary artery and the pressure gradient of the left ventricular outflow tract. The cardiac catheterization was performed via a right radial artery approach and a total of 200 mL of 370 mg I/mL iopromide was injected. The patient developed contrast-induced encephalopathy following the cardiac catheterization procedure, displaying severe headache, cortical blindness and neuropsychiatric symptom as the main clinical manifestations. The patient was then given symptomatic and supportive treatment, including decreasing intracranial pressure, analgesics and sedatives, and the patient recovered.

Novel biomarkers for post-contrast acute kidney injury identified from long non-coding RNA expression profiles.

Background: Post-contrast acute kidney injury (PC-AKI) is a severe complication of cardiac catheterization. Emerging evidence indicated that long non-coding RNAs (lncRNAs) could serve as biomarkers for various diseases. However, the lncRNA expression profile and potential biomarkers in PC-AKI remain unclear. This study aimed to investigate novel lncRNA biomarkers for the early detection of PC-AKI. Methods: lncRNA profile in the kidney tissues of PC-AKI rats was evaluated through RNA sequencing. Potential lncRNA biomarkers were identified through human-rat homology analysis, kidney and blood filtering in rats and verified in 112 clinical samples. The expression patterns of the candidate lncRNAs were detected in HK-2 cells and rat models to evaluate their potential for early detection. Results: In total, 357 lncRNAs were found to be differentially expressed in PC-AKI. We identified lnc-HILPDA and lnc-PRND were conservative and remarkably upregulated in both kidneys and blood from rats and the blood of PC-AKI patients; these lncRNAs can precisely distinguish PC-AKI patients (area under the curve (AUC) values of 0.885 and 0.875, respectively). The combination of these two lncRNAs exhibited improved accuracy for predicting PC-AKI, with 100% sensitivity and 83.93% specificity. Time-course experiments showed that the significant difference was first noted in the blood of PC-AKI rats at 12 h for lnc-HILPDA and 24 h for lnc-PRND. Conclusion: Our study revealed that lnc-HILPDA and lnc-PRND may serve as the novel biomarkers for early detection and profoundly affect the clinical stratification and strategy guidance of PC-AKI.

Dynamic Perfusion Computed Tomography and Apparent Diffusion Coefficient as Potential Markers for Poorly Differentiated Pancreatic Adenocarcinoma.

INTRODUCTION: Tumor grade, one of the most important risk factors for survival, is routinely determined after examining the biopsy material or a surgically removed specimen. The aim of the study was to analyze computed tomography (CT) perfusion parameters and diffusion-weighted imaging apparent diffusion coefficient (ADC) values in pancreatic ductal adenocarcinoma (PDAC) and to establish the diagnostic value of these modalities determining the tumor grade. MATERIALS AND METHODS: A prospective clinical study included 56 subjects with PDAC. All the patients had a local perfusion assessment and ADC measurement of the tumor. For the prediction of poor tumor differentiation sensitivity, specificity, positive, and negative predictive values for each perfusion CT and ADC parameters based on cutoff values from ROC analysis were calculated. RESULTS: Mean transit time (MTT) and ADC values were found to be independent prognosticators for the presence of G3 PDAC. MTT and ADC at the cutoff of 17.37 s and 1.15 × 10-3 mm2/s, respectively, appeared to be significant parameters discriminating against the differentiation grade of PDAC. If both values exceeded the defined cutoff point, the estimated probability for the presence of G3 PDAC was 89.29%. CONCLUSION: The MTT parameter, calculated with the deconvolution method, and the ADC value may serve as effective independent prognosticators identifying poorly differentiated PDAC.

Combined rare anatomic variants: persistent primitive olfactory artery and azygos pericallosal artery.

The persisting primitive olfactory artery (PPOA) is a rare anatomic variation of the anterior cerebral artery (ACA), being encountered in less than 1% of cases. Different morphological types were reported previously. In type 3, only once reported previously, the PPOA gives off two branches, a nasal one which courses in the olfactory sulcus to supply the territory of the anterior ethmoidal artery, and the callosomarginal artery. It is reported here a combination of rare anatomic variants found in a 71-year-old male patient investigated by computed tomography angiography. A left PPOA left the A1 segment of the ACA and was classified as subtype 3b, as its branches were the nasal one and a frontal trunk, not the callosomarginal artery. That PPOA had a characteristic hairpin turn applied on the anterior fossa floor. The ACA continued as azygos pericallosal artery, which is also a rare finding. As the nasal branch of the PPOA and its hairpin turn is closely related to the anterior fossa floor, such variant should be carefully documented when combined approaches of the skull base are planned by rhinologists and neurosurgeons.

Iodine-related attenuation in contrast-enhanced dual-energy computed tomography in small-sized solid-type lung cancers is associated with the postoperative prognosis.

BACKGROUND: To investigate the correlation between iodine-related attenuation in contrast-enhanced dual-energy computed tomography (DE-CT) and the postoperative prognosis of surgically resected solid-type small-sized lung cancers. METHODS: We retrospectively reviewed the DE-CT findings and postoperative course of solid-type lung cancers ≤3 cm in diameter. After injection of iodinated contrast media, arterial phases were scanned using 140-kVp and 80-kVp tube voltages. Three-dimensional iodine-related attenuation (3D-IRA) of primary tumors at the arterial phase was computed using the "lung nodule" application software. The corrected 3D-IRA normalized to the patient's body weight and contrast medium concentration was then calculated. RESULTS: A total of 120 resected solid-type lung cancers ≤3 cm in diameter were selected for analysis (82 males and 38 females; mean age, 67 years). During the observation period (median, 47 months), 32 patients showed postoperative recurrence. Recurrent tumors had significantly lower 3D-IRA and corrected 3D-IRA at early phase compared to non-recurrent tumors (p = 0.046 and p = 0.027, respectively). The area under the receiver operating characteristic curve for postoperative recurrence was 0.624 for the corrected 3D-IRA at early phase (p = 0.025), and the cutoff value was 5.88. Kaplan-Meier curves for disease-free survival indicated that patients showing tumors with 3D-IRA > 5.88 had a significantly better prognosis than those with tumors showing 3D-IRA < 5.88 (p = 0.017). CONCLUSIONS: The 3D-IRA of small-sized solid-type lung cancers on contrast-enhanced DE-CT was significantly associated with postoperative prognosis, and low 3D-IRA tumors showed a higher TNM stage and a significantly poorer prognosis.

Anatomic variations of the superficial temporal artery.

The superficial temporal artery (STA) is a terminal branch of the external carotid artery. It is commonly described as coursing posterior to the mandibular condyle and over the posterior zygomatic root (PZR) and then dividing terminally into parietal and frontal branches. However, possible variations of the main trunk of the STA have seemingly been overlooked. This study retrospectively examined the archived head tomography angiograms of 43 patients to determine the morphology and topography of the STA prior to its terminal bifurcation. In 79% of patients, the STA topography related to the mandibular condyle was bilaterally symmetrical, either retrocondylar (65.1%) or laterocondylar (13.6%). The parietal branch was sometimes absent unilaterally (16.3%) or bilaterally (9.3%). In 2/43 cases, the frontal branch of the STA was unilaterally absent. When both terminal branches were present, the bifurcation was retrocondylar or immediately above the PZR when on the PZR, or the terminal division of the STA was high above the PZR. In 88.4% of the STAs, different patterns of kinking and coiling were documented, including retrocondylar kinks (27.9%), laterocondylar kinks (20.9%), kinks placed on the PZR (81.4%) and variably oriented suprazygomatic kinks (32.6%). Five of the 86 STAs were coiled, one retrocondylar, one laterocondylar, and three other placed on the PZR. Two cases showed unilateral pseudoaneurysms of the STA, one above the PZR and the other on the temporomandibular joint. The STA is surgically important; therefore, the number of anatomical studies of the STA should increase.

Transcatheter arterial embolization in abdominal blunt trauma with active mesenteric bleeding: case series and review of literature.

PURPOSE: To evaluate the safety and effectiveness of transcatheter arterial embolization (TAE) in treating traumatic mesenteric injuries with active bleeding, to report the outcome in a case series, and to compare the results with the existing data. METHODS: All consecutive patients with active mesenteric bleeding due to blunt abdominal trauma referred to a level-one Trauma Center and treated by TAE were included; the related demographic and medical data were retrospectively reported. A literature review was conducted; all reported cases were collected and analysed together with our case series. A univariate analysis of risk factors for TAE failure, bowel necrosis, complication and length of stay was performed. RESULTS: Four consecutive patients were included. Technical success was 100%. One patient developed colon ischemia after the procedure and underwent surgical treatment; another presented transient mild renal failure and late respiratory failure. No 30-day mortality was reported. These results are consistent with those reported in literature. The analysis of our cases together with case collected from literature resulted in a case series of 25 patients. Univariate analysis showed colon as site of bleeding as a significant risk factor for bowel necrosis and older age as a significant risk factor for longer length of stay. TAE failure was not significantly associated neither with a higher complication rate nor with a higher length of stay. CONCLUSION: TAE is a safe and effective procedure to control mesenteric bleeding, thus should be considered, in selected cases and in appropriate setting, as an alternative to emergency surgery.

A randomized comparison of a novel iopromide-based paclitaxel-coated balloon Shenqi versus SeQuent Please for the treatment of in-stent restenosis.

BACKGROUND: Treatment of coronary in-stent restenosis (ISR) remains challenging in contemporary clinical applications. Drug-coated balloon (DCB) angioplasty offers an effective treatment for ISR. Shenqi is a novel iopromide-based paclitaxel-coated balloon and its clinical safety, effectiveness and angiographic efficacy in patients with ISR have not been investigated. METHODS: A total of 216 subjects with the first occurrence of ISR at 11 investigational sites in China were randomly allocated in a 1:1 fashion to treatment with DCB SeQuent Please or Shenqi. Clinical follow-up was planned at 1, 6, 9 and 12 months, and angiographic follow-up was planned at 9 months. The study was powered for the primary endpoint of 9-month in-segment late loss. RESULTS: At 9-month follow-up, the in-segment late loss was 0.29 ± 0.43 mm with Shenqi versus 0.30 ± 0.46 mm with SeQuent Please, and the one-sided 97.5% upper confidence limit of the difference was 0.14 mm, achieving noninferiority of Shenqi compared with SeQuent Please (P = 0.002). In total, 12 patients developed target lesion failure (TLF) in the Shenqi group compared with 16 patients in the SeQuent Please group (10.91% versus 15.09%; P = 0.42) within 1 year. TLF was mainly driven by target lesion revascularization (9.09%) followed by target vessel-related myocardial infarction (1.82%) and cardiovascular death (0.91%) in the Shenqi group. CONCLUSIONS: Shenqi DCB was noninferior to SeQuent Please DCB for the primary endpoint of 9-month in-segment late loss. Shenqi DCB may become an attractive alternative treatment for patients with coronary ISR, withholding the need for additional stent implantation.