Publications by authors named "Xinwei Han"

301 Publications

Effect of laparoscopic angle of His reconstruction in the treatment of patients with gastroesophageal reflux disease and hiatal hernia.

Chin Med J (Engl) 2022 Aug 11. Epub 2022 Aug 11.

Department of Intervention, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan 450052, China.

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http://dx.doi.org/10.1097/CM9.0000000000002211DOI Listing
August 2022

3.0-T closed MR-guided microwave ablation for HCC located under the hepatic dome: a single-center experience.

Int J Hyperthermia 2022 Dec;39(1):1044-1051

Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Purpose: To analyze the clinical safety and efficacy of 3.0-T closed MR-guided microwave ablation (MWA) for the treatment of HCC located under the hepatic dome.

Methods: From May 2018 to October 2020, 49 patients with 74 HCCs located under the hepatic dome underwent MWA using 3.0-T closed MR guidance. The technical success rate, operative time, complete ablation (CA) rate, complications, local tumor progression (LTP), tumor-free survival (TFS) and overall survival (OS) were examined. Routine blood analysis, liver/kidney function and alpha fetoprotein (AFP) and protein induced by vitamin k absent or antagonist (PIVKA) levels were compared before and 2 months after MWA.

Results: All patients underwent MWA successfully, including 10 patients who underwent general anesthesia. The technical success rate was 100% without major complications. The CA rate was 95.9% (71/74) at the 2-month evaluation. The LTP rate was 2.7% during the median follow-up of 17.8 months (range: 4-43 months); the 6-, 12-, 18-month TFS rates were 97.8, 90.6, 68.1%, respectively, and the 6-, 12-, 18-month OS rates were 100, 97.6, 92.1%, respectively. There were no significant changes in routine blood tests and liver/kidney function ( > 0.05), while the AFP and PIVKA level decreased significantly at 2 months ( < 0.05).

Conclusion: 3.0-T MR-guided MWA is safe and feasible for HCC lesions located under the hepatic dome.
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http://dx.doi.org/10.1080/02656736.2022.2107717DOI Listing
December 2022

Transcatheter arterial chemoembolization is safe and effective for patients with late-stage or recurrent oral carcinoma.

Front Oncol 2022 22;12:831583. Epub 2022 Jul 22.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Objective: We reported the long-term outcomes of transcatheter chemoembolization (TACE) for patients with late-stage or recurrent oral carcinoma.

Methods: This retrospective study enrolled 18 patients with late-stage or recurrent oral carcinoma between December 2015 and April 2021. The tumor-feeding artery was catheterized, and cisplatin/oxaliplatin and 5-FU/raltitrexed were infused with embolization using polyvinyl alcohol or gelatin sponge. Computed tomography was performed at about 1, 3, and 6 months after the procedure, and every 6 months after that. During the procedure and follow-up, procedure outcomes, complications, treatment efficacy, and overall survival were analyzed.

Results: A total of 31 sessions of TACE were performed, with a technical success rate of 100%. Of 12 patients combined with oral hemorrhage, two patients showed rebleeding 35 and 37 days later, with a clinical efficiency of hemostasis of 88.9%. Mild complications were observed in 11 patients (61.1%). Severe complications or procedure-related deaths were not observed during or after the procedure. The objective response rate and disease control rate were 20.0% and 86.7%, 38.5% and 61.5%, and 25.0% and 50.0% at 1, 3, and 6 months later, respectively. Seventeen patients (94.4%) were followed up, with a median duration of 37.8 months (IQR 22.3-56.8). Nine patients died of tumor progression, one died of massive rebleeding, and one died of severe lung infection. The median overall survival was 23.8 months.

Conclusion: TACE is a safe and effective procedure with minimal invasiveness for treating late-stage or recurrent oral carcinoma. TACE can be recommended as a palliative treatment, particularly for patients with oral hemorrhage.
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http://dx.doi.org/10.3389/fonc.2022.831583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353522PMC
July 2022

A creatinine-based model for predicting recurrent bleeding after modified percutaneous transhepatic variceal embolization in patients with cirrhosis.

J Interv Med 2022 May 26;5(2):95-102. Epub 2022 Mar 26.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

Background: Patients who survive initial esophagogastric variceal bleeding (EVB) are at an increased risk of recurrent bleeding and death; however, a reliable predictive model is lacking. We aimed to develop a model for rebleeding prediction in patients with EVB after modified percutaneous transhepatic variceal embolization (PTVE) with cyanoacrylate.

Methods: A total of 122 patients with EVB who underwent PTVE from January 2015 to November 2020 were enrolled. Multivariate logistic analyses were conducted to determine independent risk factors for nomogram construction. The discrimination, calibration, and clinical utility of the nomogram were compared with the Model for End-stage Liver Disease score (MELD) and the Child-Pugh model. Risk stratification was performed according to the nomogram.

Results: Rebleeding within 3 months of PTVE occurred in 32 patients (26.2%). Independent rebleeding indicators included prior history of endoscopic therapy, Child-Pugh score, partial splenic embolization, and creatinine level. The nomogram incorporating these four predictors achieved excellent calibration and discriminatory abilities, with a concordance index of 0.85, which was confirmed to be 0.83 through bootstrapping validation. The nomogram demonstrated superior discrimination and clinical applicability than the MELD and Child-Pugh models. As shown in the Kaplan-Meier curves, high-risk patients had a high probability of rebleeding (P ​< ​0.001).

Conclusions: The creatinine-based nomogram had a superior ability to predict rebleeding after PTVE in patients with EVB. Risk stratification may help identify high-risk patients and lead to the earlier implementation of aggressive treatments and formulation of intensive follow-up plans.
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http://dx.doi.org/10.1016/j.jimed.2022.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348999PMC
May 2022

Brachytherapy Drainage Catheter and Chemotherapy for Unresectable Pancreatic Carcinoma Combined with Obstructive Jaundice.

Front Oncol 2022 14;12:941336. Epub 2022 Jul 14.

Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Most patients with advanced pancreatic cancer do not have the chance to undergo surgery or chemotherapy because of their poor conditions. Biliary drainage is a palliative treatment to restore liver function and alleviate jaundice, but most patients still face the risk of biliary obstruction in the short term after operation. The purpose of this study is to evaluate the efficacy and safety of brachytherapy drainage catheter (BDC)-combined chemotherapy in the treatment of pancreatic cancer complicated with obstructive jaundice.

Patients And Methods: From November 2017 and May 2019, 48 patients underwent the BDC or conventional drainage catheter (CDC) intervention with chemotherapy. The outcomes/endpoints analyzed were technical and clinical success, early complications, stent patency period, and survival.

Results: The technical and clinical success rates in both groups were 100%, and the early complication rates were not significantly different (P = 0.43). The median stent patency in the BDC group was significantly longer than that in the CDC group (7.8 ± 1.5 vs. 5.7 ± 0.7 months, P = 0.001), and the median overall survival period in the BDC group was prone to significant difference than that in the CDC group (9.4 ± 4.0 vs. 8.2 ± 0.3 months, P = 0.089).

Conclusion: The findings of this study show that BDC with chemotherapy was associated with better stent patency and survival. However, since the sample size was very small, large randomized controlled multicenter studies are needed to further evaluate the long-term survival effects of BDC in patients with advanced pancreatic carcinoma combined with obstructive jaundice.
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http://dx.doi.org/10.3389/fonc.2022.941336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329565PMC
July 2022

Liquid Biopsy in Pre-Metastatic Niche: From Molecular Mechanism to Clinical Application.

Front Immunol 2022 15;13:958360. Epub 2022 Jul 15.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Metastatic dissemination represents a hallmark of cancer that is responsible for the high mortality rate. Recently, emerging evidence demonstrates a time-series event-pre-metastatic niche (PMN) has a profound impact on cancer metastasis. Exosomes, cell-free DNA (cfDNA), circulating tumor cells (CTC), and tumor microenvironment components, as critical components in PMN establishment, could be monitored by liquid biopsy. Intensive studies based on the molecular profile of liquid biopsy have made it a viable alternative to tissue biopsy. Meanwhile, the complex molecular mechanism and intercellular interaction are great challenges for applying liquid biopsy in clinical practice. This article reviews the cellular and molecular components involved in the establishment of the PMN and the promotion of metastasis, as well as the mechanisms of their interactions. Better knowledge of the characteristics of the PMN may facilitate the application of liquid biopsy for clinical diagnosis, prognosis, and treatment.
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http://dx.doi.org/10.3389/fimmu.2022.958360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334814PMC
August 2022

2450-MHz microwave ablation of liver metastases under 3.0 T wide-bore magnetic resonance guidance: a pilot study.

Sci Rep 2022 Jul 25;12(1):12640. Epub 2022 Jul 25.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan, China.

To investigate the feasibility and effectiveness of 3.0 T wide-bore magnetic resonance (MR)-guided microwave ablation (MA) of liver metastases (LM). From October 2018 to May 2020, 39 patients with 63 LM were treated with 3.0 T wide-bore MR-guided 2450-MHz MA therapy. The procedure parameters, technical success, complications, biochemical index changes, local tumor response, local tumor progression (LTP), 12-month disease-free survival (DFS) and 12-month overall survival (OS) were recorded and analyzed. The mean tumor maximum diameter and total procedure time were 3.0 cm and 55.2 min, respectively. Technical success was 100%, but 5 cases (12.8%) had grade-1 complications. Alanine transaminase, aspartate transaminase and total bilirubin showed a slight transient increase on day 3 (P < 0.05) and returned to normal by day 30 (P > 0.05). The complete ablation rates for ≤ 2.5 and > 2.5 cm lesions were 100% and 92.5%, respectively. During the median follow-up of 12.0 months, the LTP rate was 4.8% (3/63), and the 12-month DFS and OS rates were 61.3% and 92.2%, respectively. 3.0 T wide-bore MR-guided MA for LM is a safe and effective approach, especially for small LM.
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http://dx.doi.org/10.1038/s41598-022-16989-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314346PMC
July 2022

SCG2: A Prognostic Marker That Pinpoints Chemotherapy and Immunotherapy in Colorectal Cancer.

Front Immunol 2022 1;13:873871. Epub 2022 Jul 1.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Fluorouracil (FU)-based chemotherapy regimens are indispensable in the comprehensive treatment of colorectal cancer (CRC). However, the heterogeneity of treated individuals and the severe adverse effects of chemotherapy results in limited overall benefit.

Methods: Firstly, Weighted gene co-expression network analysis (WGCNA) identified modules tightly associated with chemotherapy response. Then, the in-house cohort and prognostic cohorts from TCGA and GEO were subjected to Cox proportional hazards model and survival analysis to ascertain the predictable function of SCG2 on the prognosis of CRC patients. Finally, we performed experiments, functional analysis, somatic mutation, and copy number variation research to explore the biological characteristics of SCG2.

Results: We identified red and green as the modules most associated with chemotherapy response, in which SCG2 was considered a risky factor with higher expression predicting poorer prognosis. SCG2 expression in the APC non-mutation group was remarkably higher than in the mutation group. The mutation frequencies of amplified genes differed significantly between different SCG2 expression subgroups. Besides, CRC cell lines with SCG2 knockdown have reduced invasive, proliferative, and proliferative capacity. We discovered that the SCG2 high expression subgroup was the immune hot type and considered more suitable for immunotherapy.

Conclusion: This study demonstrates the clinical significance and biological characteristics of SCG2, which could serve as a promising biomarker to identify patients who may benefit from chemotherapy and immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2022.873871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283651PMC
July 2022

ALOX12: A Novel Insight in Bevacizumab Response, Immunotherapy Effect, and Prognosis of Colorectal Cancer.

Front Immunol 2022 27;13:910582. Epub 2022 Jun 27.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Colorectal cancer is a highly malignant cancer with poor prognosis and mortality rates. As the first biological agent approved for metastatic colorectal cancer (mCRC), bevacizumab was confirmed to exhibit good performance when combined with chemotherapy and immunotherapy. However, the efficacy of both bevacizumab and immunotherapy is highly heterogeneous across CRC patients with different stages. Thus, exploring a novel biomarker to comprehensively assess the prognosis and bevacizumab and immunotherapy response of CRC is of great significance. In our study, weighted gene co-expression network analysis (WGCNA) and the receiver operating characteristic (ROC) curves were employed to identify bevacizumab-related genes. After verification in four public cohorts and our internal cohort, ALOX12 was identified as a key gene related to bevacizumab response. Prognostic analysis and experiments further demonstrated that ALOX12 was closely associated with the prognosis, tumor proliferation, invasion, and metastasis. Multi-omics data analysis based on mutation and copy number variation (CNV) revealed that RYR3 drove the expression of ALOX12 and the deletion of 17p12 inhibited ALOX12 expression, respectively. Moreover, we interrogated the relationship between ALOX12 and immune cells and checkpoints. The results exhibited that high ALOX12 expression predicted a higher immune infiltration and better immunotherapy response, which was further validated in Tumor Immune Dysfunction and Exclusion (TIDE) and Subclass Mapping (SubMap) methods. Above all, our study provides a stable biomarker for clinical protocol optimization, prognostic assessment, precise treatment, and individualized treatment of CRC.
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http://dx.doi.org/10.3389/fimmu.2022.910582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271859PMC
July 2022

Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma.

Comput Struct Biotechnol J 2022 2;20:3449-3460. Epub 2022 Jul 2.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.

Background: Pharmacogenomics is crucial for individualized drug therapy and plays an increasingly vital role in precision medicine decision-making. However, pharmacogenomics-based molecular subtypes and their potential clinical significance remain primarily unexplored in lung adenocarcinoma (LUAD).

Methods: A total of 2065 samples were recruited from eight independent cohorts. Pharmacogenomics data were generated from the profiling of relative inhibition simultaneously in mixtures (PRISM) and the genomics of drug sensitivity in cancer (GDSC) databases. Multiple bioinformatics approaches were performed to identify pharmacogenomics-based subtypes and find subtype-specific properties.

Results: Three reproducible molecular subtypes were found, which were independent prognostic factors and highly associated with stage, survival status, and accepted molecular subtypes. Pharmacogenomics-based subtypes had distinct molecular characteristics: S-Ⅰ was inflammatory, proliferative, and immune-evasion; S-Ⅱ was proliferative and genetics-driven; S-III was metabolic and methylation-driven. Finally, our study provided subtype-guided personalized treatment strategies: Immune checkpoint blockers (ICBs), doxorubicin, tipifarnib, AZ628, and AZD6244 were for S-Ⅰ; Cisplatin, camptothecin, roscovitine, and A.443654 were for S-Ⅱ; Docetaxel, paclitaxel, vinorelbine, and BIBW2992 were for S-III.

Conclusion: We provided a novel molecular classification strategy and revealed three pharmacogenomics-based subtypes for LUAD patients, which uncovered potential subtype-related and patient-specific therapeutic strategies.
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http://dx.doi.org/10.1016/j.csbj.2022.06.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271977PMC
July 2022

Preliminary outcomes of raltitrexed eluting bead-transarterial chemoembolization using Callispheres® beads for gastrointestinal adenocarcinoma liver metastasis.

World J Surg Oncol 2022 Jul 12;20(1):229. Epub 2022 Jul 12.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No.1, East Jian She Road, Zhengzhou, 450052, China.

Background: Drug-eluting bead transarterial chemoembolization (DEB-TACE) with Callispheres® beads (CB) is currently used in the treatment of hepatocellular carcinoma. However, clinical data regarding DEB-TACE using raltitrexed-eluting CB for gastrointestinal adenocarcinoma liver metastases (GALM) treatment is limited. We aimed to report the preliminary outcomes of DEB-TACE using CB in unresectable GALM patients.

Methods: This retrospective study enrolled unresectable GALM patients who were treated with DEB-TACE using raltitrexed-eluting CB from October 2018 to October 2021. Totally, 25 patients, 18 males and 7 females, mean age 66.8±9.5 years, were continuously enrolled. Postoperative treatment response, survival rates, and complication were calculated during the procedure and follow-up.

Results: Twenty-four patients were technically successful, with a technical success rate of 96.0%. The 3-month overall response rate and disease control rate were 21.7% and 73.9%, and 6-month overall response rate and disease control rate were 30.0% and 65.0%. The median survival time from diagnosis of GALM was 31.3 months. The median survival time and median PFS from first DEB-TACE was 21.3 months (95% confidence interval 9.1-33.5) and 10.7 months (3.7-17.7), respectively. Main adverse events included abdominal pain (36.0%), fever (12.0%), and nausea/vomiting (28.0%) after DEB-TACE. No treatment-related deaths and grade 3 or grade 4 adverse events were observed.

Conclusions: DEB-TACE using raltitrexed eluting CB was demonstrated as a safe and efficient alternative choice for GALM.
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http://dx.doi.org/10.1186/s12957-022-02696-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277920PMC
July 2022

Crucial Roles of LncRNAs-Mediated Autophagy in Breast Cancer.

Int J Med Sci 2022 21;19(6):1082-1092. Epub 2022 Jun 21.

Tai Zhou Central Hospital (Taizhou University Hospital), No.999 Donghai Road, Jiaojiang District, Taizhou, Zhejiang, 318000, China.

Breast cancer remains a worldwide public health issue. LncRNA and autophagy respectively or simultaneously, get involved in cellular and molecular processes of many different cancers, including genesis, metastasis, and deterioration of breast cancer and other malignant tumors. In this review, relevant studies have been summarized, and we have found that lncRNA-mediated autophagy in luminal A breast cancer, luminal B breast cancer, HER-2 positive breast cancer, and basal-like breast cancer may play an important role in mediating drug resistance sensitivity. LncRNAs target genes and affect different signaling pathways to a complex network, which attenuates the occurrence and development of primary breast cancer by coordinating autophagy. Abnormal expression of LncRNA may lead to dysregulation of autophagy, resulting in tumor genesis, expansion, and resistance to anti-tumor therapy. Targeting specific lncRNAs for autophagy regulation may conduct as a bio-marker for reliable diagnosis and prognosis treatment of breast cancer or provide a promising therapeutic strategy.
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http://dx.doi.org/10.7150/ijms.72621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254371PMC
July 2022

Stent-in-stent technique under fluoroscopy for removal of embedded esophageal stent: a retrospective case series.

Quant Imaging Med Surg 2022 Jul;12(7):3813-3820

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Treatment of complications after esophageal stent placement and methods for removal of stents need to be improved. The purpose of this study was to evaluate the safety and efficacy of stent-in-stent (SIS) removal of esophageal stent under fluoroscopy.

Methods: This study analyzed the clinical data of consecutive patients undergoing esophageal stent removal by the SIS technique under fluoroscopy. The procedure was performed under local anesthesia on conscious sedated patients. Under fluoroscopy, a second esophageal stent was released within the lumen of the first esophageal stent. The second stent was larger than the first, with both ends protruding 1-2 cm beyond the ends of the first stent. Four weeks later, both esophageal stents were removed by the SIS technique under fluoroscopy. All procedures were performed by the same interventional radiologist (with >10 years of experience).

Results: A total of 25 patients were treated by the SIS removal technique. In 23 patients, the first esophageal stent was easily removed by the SIS technique; in the other 2 patients, stent fracture occurred, and some residual nitinol wire had to be removed endoscopically. No serious complications occurred in any patient.

Conclusions: The SIS removal technique appears to be a safe and effective method for removal of embedded esophageal metallic stents.
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http://dx.doi.org/10.21037/qims-21-1039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246751PMC
July 2022

Vacuum sealing drainage combined with naso-intestinal and gastric decompression tubes for the treatment of esophagogastrostomy neck fistula.

J Cardiothorac Surg 2022 Jun 13;17(1):153. Epub 2022 Jun 13.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, Henan Province, China.

Objective: To evaluate the clinical results of the vacuum sealing drainage (VSD) combined with a naso-intestinal nutritional tube (NIT) and a gastric decompression tube (GDT) for the treatment of esophagogastrostomy neck fistula (ENF).

Methods: From January 2018 to October 2020, twenty patients (13 men and 7 women, ages 46-72) with ENF secondary to esophagogastrostomy were treated with VSD combined with NIT and GDT. Technical and clinical success rates, the incidence of early/late complications, the time of fistula closure (TFC) and therapy-related indicators were analyzed. The Karnofsky score and Eastern Cooperative Oncology Group (ECOG) score were compared before and after triple treatment.

Results: Technical and clinical success rates were 100% and 85%, respectively. Early complications occurred in 5/20 (25%) patients, and late complications occurred in 8/20 (40%) patients. The median TFC was 18 days (range 10-23). All therapy-related indicators were normalized posttreatment. The Karnofsky score and ECOG score after treatment were significantly different compared with pretreatment scores (p < 0.001).

Conclusion: VSD combined with NIT and GDT is a safe and effective strategy for ENF, while severe strictures warrant further research.
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http://dx.doi.org/10.1186/s13019-022-01883-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9195471PMC
June 2022

Transarterial chemoembolization of unresectable renal cell carcinoma with doxorubicin-loaded CalliSpheres drug-eluting beads.

Sci Rep 2022 05 17;12(1):8136. Epub 2022 May 17.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No.1, East Jian She Road, Zhengzhou, 450052, China.

The safety and efficacy of drug-eluting beads transarterial chemoembolization (DEB-TACE) for unresectable renal cell carcinoma (RCC) still unknown. We aimed to assess the feasibility, safety and clinical efficacy of DEB-TACE with doxorubicin-loaded CalliSpheres beads (CB) in patients with unresectable RCC. Between 2016 and 2020, thirty-five patients with unresectable RCC underwent DEB-TACE with doxorubicin-loaded CB. The objective response rate (ORR) was the primary endpoint, and overall survival (OS) and progression-free survival (PFS) were the secondary endpoints. Fifteen-seven times of DEB-TACE were performed in 35 patients using doxorubicin-loaded (median 60 mg) CB. Fifteen patients underwent an additional session of DEB-TACE, with intervals of 1 to 1.5 months. Twenty-one patients underwent transarterial infusion with cisplatin or oxaliplatin before DEB-TACE. The median follow-up time was 9.0 months (Range 1.8-43.6 months). ORR and DCR were 47.1% and 94.1%, 29.0% and 87.1%, 23.1% and 84.6% respectively at 1-, 3-, and 6- months after DEB-TACE. The median PFS was 21.4 months, and the 3-, 6- and 12- month PFS rates were 84.7%, 73.7% and 62.3%, respectively. The median OS was 24.6 months, and the 3-, 6- and 12- month OS rates were 93.9%, 87.6% and 65.2%, respectively. There were no treatment-related deaths or severe adverse events of grade 3 or more. In conclusion, DEB-TACE with doxorubicin-loaded CB is a safe, feasible and effective palliative treatment option for patients with unresectable RCC.
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http://dx.doi.org/10.1038/s41598-022-12334-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9113996PMC
May 2022

Drug-Eluting Embolics Chemoembolization for the Management of Recurrent or Advanced Head and Neck Cancer.

J Vasc Interv Radiol 2022 Aug 13;33(8):949-955. Epub 2022 May 13.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.

Purpose: To characterize the safety, tolerability, and efficacy of chemoembolization using drug-eluting embolic (DEE) microspheres in patients with recurrent and advanced head and neck cancer.

Materials And Methods: In this retrospective study, 32 patients (mean age, 57.2 years ± 2.8; 17 women) with recurrent (n = 16) and advanced (n = 16) head and neck cancer were treated with chemoembolization using DEE microspheres loaded with doxorubicin. Treatment response, overall survival, local progression-free survival, and adverse events were evaluated.

Results: At 6 months after the procedure, the objective response and disease control rates were 25% and 69%, respectively. The median overall survival and local progression-free survival were 14.5 and 13.6 months, respectively. Seven (22%) patients experienced adverse events after the chemoembolization procedure. All the adverse events were related to postembolization syndrome, including vomiting and nausea (n = 1), pyrexia (n = 2), and localized pain (n = 7). No severe adverse events or procedure-related deaths were observed.

Conclusions: Chemoembolization using DEE microspheres was safe and tolerable in patients with recurrent and advanced head and neck cancer.
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http://dx.doi.org/10.1016/j.jvir.2022.05.002DOI Listing
August 2022

Intraoperative cone beam computed tomography of tracheal stenting for stenosis and fistula diseases: a retrospective cohort study.

Quant Imaging Med Surg 2022 May;12(5):2709-2720

Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Angiographic computed tomography (CT) is useful in various medical contexts, but little research has been presented regarding the application of cone beam CT (CBCT) in airway stenting. This study set out to evaluate the clinical feasibility of using CBCT in airway stent placement in a single-center retrospective cohort.

Methods: A total of 228 patients with stenosis or fistula diseases were treated with metallic airway stents in the First Affiliated Hospital of Zhengzhou University from January 1, 2015, to December 31, 2018. Of them, 128 patients underwent fluoroscopy-guided airway stenting. CBCT scanning was performed on the other 100 patients during and after treatment, and their images were compared with those from postoperative multidetector CT (MDCT). The outcomes and complications in the CBCT-guided and fluoroscopy-guided groups were also assessed via Pearson's χ test or Fisher's exact test.

Results: Tracheal stenting was performed successfully on the first attempt for 90 patients in the CBCT-guided group and 123 patients in the fluoroscopy-guided group. The mean measured diameters of the central airway in the CBCT images and MDCT images were 18.2±2.81 and 19.0±2.33 mm, respectively, and the mean lengths were 58.7±16.82 and 58.5±17.06 mm, respectively. In the CBCT-guided group and the fluoroscopy-guided group, the mean scores for visibility of the distal bronchus were 3.7±0.49 and 3.9±0.34, respectively; the mean scores for the pulmonary parenchyma were 3.3±0.71 and 3.9±0.31, respectively; and the mean scores for the airway above the upper stent graft were 1.8±0.41 and 4.0±0.20, respectively. Two of the three anatomical areas were reproduced in a diagnostically relevant way. The major complications rate was 7% and 19% in the CBCT-guided and fluoroscopy-guided groups, respectively.

Conclusions: CBCT produces images with sufficient quality to replace MDCT as a reasonable control measure after stent implantation, and its use during surgery reduces complications relating to airway stent placement.
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http://dx.doi.org/10.21037/qims-21-858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014159PMC
May 2022

Customised Y-shaped self-expandable covered metallic stent with a dead end for the treatment of bronchopleural fistula.

Thorax 2022 Apr 21. Epub 2022 Apr 21.

Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

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http://dx.doi.org/10.1136/thoraxjnl-2021-218080DOI Listing
April 2022

TP53 /KRAS Co-Mutations Create Divergent Prognosis Signatures in Intrahepatic Cholangiocarcinoma.

Front Genet 2022 25;13:844800. Epub 2022 Mar 25.

Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Due to high invasiveness and heterogeneity, the morbidity and mortality of intrahepatic cholangiocarcinoma (ICC) remain unsatisfied. Recently, the exploration of genomic variants has decoded the underlying mechanisms of initiation and progression for multiple tumors, while has not been fully investigated in ICC. We comprehensively analyzed 899 clinical and somatic mutation data of ICC patients from three large-scale cohorts. Based on the mutation landscape, we identified the common high-frequency mutation genes (FMGs). Subsequently, the clinical features, prognosis, tumor mutation burden (TMB), and pharmacological landscape from patients with different mutation carriers were further analyzed. We found TP53 and KRAS were the common FMGs in the three cohorts. Kaplan-Meier survival curves and univariate and multivariate analysis displayed that TP53 and KRAS mutations were associated with poor prognosis. Considering the co-mutation phenomenon of TP53 and KRAS, we stratified patients into "Double-WT," "Single-Hit," and "Double-Hit" phenotypes by mutation status. Patients with the three phenotypes showed significant differences in the mutation landscape. Additionally, compared with "Double-WT" and "Single-Hit" phenotypes, patients with "Double-Hit" presented a dismal prognosis and significantly high TMB. Through chemotherapy sensitivity analysis, we identified a total of 30 sensitive drugs for ICC patients, of which 22 were drugs sensitive to "Double-WT," 7 were drugs sensitive to "Double-Hit," and only one was a drug sensitive to "Single-Hit." Our study defined a novel mutation classification based on the common FMGs, which may contribute to the individualized treatment and management of ICC patients.
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http://dx.doi.org/10.3389/fgene.2022.844800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990229PMC
March 2022

Development and Validation of Ischemic Events Related Signature After Carotid Endarterectomy.

Front Cell Dev Biol 2022 17;10:794608. Epub 2022 Mar 17.

Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Ischemic events after carotid endarterectomy (CEA) in carotid artery stenosis patients are unforeseeable and alarming. Therefore, we aimed to establish a novel model to prevent recurrent ischemic events after CEA. Ninety-eight peripheral blood mononuclear cell samples were collected from carotid artery stenosis patients. Based on weighted gene co-expression network analysis, we performed whole transcriptome correlation analysis and extracted the key module related to ischemic events. The biological functions of the 292 genes in the key module were annotated via GO and KEGG enrichment analysis, and the protein-protein interaction (PPI) network was constructed via the STRING database and Cytoscape software. The enrolled samples were divided into train ( = 66), validation ( = 28), and total sets ( = 94). In the train set, the random forest algorithm was used to identify critical genes for predicting ischemic events after CEA, and further dimension reduction was performed by LASSO logistic regression. A diagnosis model was established in the train set and verified in the validation and total sets. Furthermore, fifty peripheral venous blood samples from patients with carotid stenosis in our hospital were used as an independent cohort to validation the model by RT-qPCR. Meanwhile, GSEA, ssGSEA, CIBERSORT, and MCP-counter were used to enrichment analysis in high- and low-risk groups, which were divided by the median risk score. We established an eight-gene model consisting of , , , , , , , and . The ROC-AUCs and PR-AUCs of the train, validation, total, and independent cohort were 0.891 and 0.725, 0.826 and 0.364, 0.869 and 0.654, 0.792 and 0.372, respectively. GSEA, ssGSEA, CIBERSORT, and MCP-counter analyses further revealed that high-risk patients presented enhanced immune signatures, which indicated that immunotherapy may improve clinical outcomes in these patients. An eight-gene model with high accuracy for predicting ischemic events after CEA was constructed. This model might be a promising tool to facilitate the clinical management and postoperative surveillance of carotid artery stenosis patients.
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http://dx.doi.org/10.3389/fcell.2022.794608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8969028PMC
March 2022

Retraction notice to "MiR-29b aggravates lipopolysaccharide-induced endothelial cells inflammatory damage by regulation of NF-κB and JNK signaling pathways" [Biomed. Pharmacother. 99 (2018) 451-461].

Biomed Pharmacother 2022 07 25;151:112859. Epub 2022 Mar 25.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.

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http://dx.doi.org/10.1016/j.biopha.2022.112859DOI Listing
July 2022

The zone II aorta is not a forbidden zone for occlusion in women with morbidly adherent placenta.

Arch Gynecol Obstet 2022 Mar 23. Epub 2022 Mar 23.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan, People's Republic of China.

Aim: To evaluate the safety and efficacy of balloon occlusion at the Zone II aorta for the management of morbidly adherent placenta.

Methods: From September 2015 to October 2018, a total of 80 consecutive patients who were prenatally diagnosed with morbidly adherent placenta were assigned into two groups: the balloon occlusion group (n = 40) and the non-balloon occlusion group (n = 40).The intraoperative estimated blood loss, blood transfusion, urine output, serum creatinine, blood urea nitrogen and hysterectomy rate were recorded and compared between the two groups.

Results: The estimated blood loss in the balloon occlusion group was significantly lower than that in the non-balloon occlusion group (811.75 ± 299.93 ml vs 1529.75 ± 808.01 ml, P < 0.001). The median amount of packed RBCs transfused in the balloon occlusion group and non-balloon occlusion group was 0 U and 2 U, respectively (P = 0.001). The women in the former group had a lower blood transfusion rate than those in the latter group (30% vs 57.5%, P = 0.013). Hysterectomy occurred in none in the balloon occlusion group but in six patients in the non-balloon occlusion group (P = 0.011).

Conclusion: The middle abdominal aorta (Zone II) is not a forbidden zone for occlusion as long as the single occlusion time is limited to 15 min. Balloon occlusion at the Zone II aorta can effectively reduce blood loss, transfusion requirements and hysterectomy rates in patients with morbidly adherent placenta.
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http://dx.doi.org/10.1007/s00404-021-06302-5DOI Listing
March 2022

Multi-omics landscape and clinical significance of a -driven immune signature: Implications for risk stratification and frontline therapies in pancreatic cancer.

Comput Struct Biotechnol J 2022 2;20:1154-1167. Epub 2022 Mar 2.

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.

mutation was recently implicated in promoting invasion and poor prognosis of pancreatic cancer (PACA) by regulating the tumor immune microenvironment. However, -driven immune landscape and clinical significance remain elusive. In this study, we applied the consensus clustering and weighted correlation network analysis (WGCNA) to identify two heterogeneous immune subtypes and immune genes. Combined with -driven genes determined by mutation status, a -driven immune signature (SDIS) was developed in ICGC-AU2 (microarray data) via machine learning algorithm, and then was validated by RNA-seq data (TCGA, ICGC-AU and ICGC-CA) and microarray data (GSE62452 and GSE85916). The high-risk group displayed a worse prognosis, and multivariate Cox regression indicated that SDIS was an independent prognostic factor. In six cohorts, SDIS also displayed excellent accuracy in predicting prognosis. Moreover, the high-risk group was characterized by higher frequencies of / mutations and deletion, superior immune checkpoint molecules expression and more sensitive to chemotherapy and immunotherapy. Meanwhile, the low-risk group was significantly enriched in metabolism-related pathways and suggested the potential to target tumor metabolism to develop specific drugs. Overall, SDIS could robustly predict prognosis in PACA, which might serve as an attractive platform to further tailor decision-making in chemotherapy and immunotherapy in clinical settings.
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http://dx.doi.org/10.1016/j.csbj.2022.02.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8908051PMC
March 2022

Integrated Analysis of Multi-Omics Alteration, Immune Profile, and Pharmacological Landscape of Pyroptosis-Derived lncRNA Pairs in Gastric Cancer.

Front Cell Dev Biol 2022 25;10:816153. Epub 2022 Feb 25.

Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Recent evidence demonstrates that pyroptosis-derived long non-coding RNAs (lncRNAs) have profound impacts on the initiation, progression, and microenvironment of tumors. However, the roles of pyroptosis-derived lncRNAs (PDLs) in gastric cancer (GC) remain elusive. We comprehensively analyzed the multi-omics data of 839 GC patients from three independent cohorts. The previous gene set enrichment analysis embedding algorithm was utilized to identify PDLs. A gene pair pipeline was developed to facilitate clinical translation qualitative relative expression orders. The LASSO algorithm was used to construct and validate a pyroptosis-derived lncRNA pair prognostics signature (PLPPS). The associations between PLPPS and multi-omics alteration, immune profile, and pharmacological landscape were further investigated. A total of 350 PDLs and 61,075 PDL pairs in the training set were generated. Cox regression revealed 15 PDL pairs associated with overall survival, which were utilized to construct the PLPPS model the LASSO algorithm. The high-risk group demonstrated adverse prognosis relative to the low-risk group. Remarkably, genomic analysis suggested that the lower tumor mutation burden and gene mutation frequency (e.g., , , and ) were found in the high-risk group patients. The copy number variants were not significantly different between the two groups. Additionally, the high-risk group possessed lower immune cell infiltration abundance and might be resistant to a few chemotherapeutic drugs (including cisplatin, paclitaxel, and gemcitabine). PDLs were closely implicated in the biological process and prognosis of GC, and our PLPPS model could serve as a promising tool to advance prognostic management and personalized treatment of GC patients.
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http://dx.doi.org/10.3389/fcell.2022.816153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8916586PMC
February 2022

Establishing a jugular-femoral venous route for recanalization of complicated inferior vena cava in Budd-Chiari Syndrome after transfemoral access failure.

Sci Rep 2022 03 10;12(1):3903. Epub 2022 Mar 10.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No.1, East Jian She Road, Zhengzhou, 450052, China.

Recanalization of inferior vena cava (IVC) with complete obstruction, old thrombosis or long segmental stenosis/obstruction (complicated IVC) via transfemoral access may fail in patients with Budd-Chiari syndrome (BCS). In this study, 34 consecutive patients with BCS underwent recanalization of complicated IVC occlusion via jugular-femoral venous (JFV) route establishment. BCS with complicated IVC was detected by reviewing preoperative color Doppler ultrasonography or computed tomography (CT) venography, and confirmed by intraoperative venography. Clinical data on technical success, complications, and follow-up outcomes were analyzed. Except for one patient received surgical repair of rupture IVC after recanalization, technical success of IVC recanalization was achieved in remaining 33 (97.1%) patients. No perioperative deaths was found. Three complications were observed during recanalization, for a complication rate of 8.8%. Bleeding of the femoral vein was observed in one patient, and two patients showed bleeding of IVC. The IVC lesion diameter and blood flow of the distal IVC increased significantly after the procedure. Twenty-four patients (77.4%) were clinically cured, and four patients (12.9%) showed clinical improvement. The 1-year, 3-year, 5-year primary patency rates were 85.9%, 76.4% and 70.0%, respectively. The 5-year secondary patency rate was 96.8%. There were three deaths during follow up, and the 5-year survival rate was 90.0%. In conclusion, JFV route establishment and angioplasty for complicated IVC is safe and effective for patients with BCS after transfemoral access failure.
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http://dx.doi.org/10.1038/s41598-022-07935-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8913740PMC
March 2022

Gene Expression Profile Reveals a Prognostic Signature of Non-MSI-H/pMMR Colorectal Cancer.

Front Cell Dev Biol 2022 17;10:790214. Epub 2022 Feb 17.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Studies have demonstrated that non-MSI-H/pMMR colorectal cancer (CRC) has a worse prognosis and relapse rate than microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) CRC. Hence, searching for a novel tool to advance the prognostic management of non-MSI-H/pMMR CRC is vital. In this study, using three independent public cohorts and a clinical in-house cohort, we developed and validated a microsatellite stable-associated signature (MSSAS). The initial signature establishment was performed in GSE39582 ( = 454). This was followed by independent validation of this signature in The Cancer Genome Atlas-CRC ( = 312), GSE39084 ( = 54), and in-house cohort ( = 146). As a result, MSSAS was proven to be an independent risk factor for overall survival and relapse-free survival in non-MSI-H/pMMR CRC. Receiver operating characteristic analysis showed that MSSAS had a stable and accurate performance in all cohorts for 1, 3, and 5 years, respectively. Further analysis suggested that MSSAS performed better than age, gender, and the T, N, M, and AJCC stages, adjuvant chemotherapy, tumor mutation burden, neoantigen, and 53, , , and mutations. The clinical validation was executed to further ensure the robustness and clinical feasibility of this signature. In conclusion, MSSAS might be a robust and promising biomarker for advancing clinical management of non-MSI-H/pMMR CRC.
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http://dx.doi.org/10.3389/fcell.2022.790214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891566PMC
February 2022

and as Diagnostic Markers for Abdominal Aortic Aneurysm and Associated With Immune Infiltration.

Front Cardiovasc Med 2022 9;9:781207. Epub 2022 Feb 9.

Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Formation and rupture of abdominal aortic aneurysm (AAA) is fatal, and the pathological processes and molecular mechanisms underlying its formation and development are unclear. Perivascular adipose tissue (PVAT) has attracted extensive attention as a newly defined secretory organ, and we aim to explore the potential association between PVAT and AAA.

Methods: We analyzed gene expression and clinical data of 30 PVAT around AAA and 30 PVAT around normal abdominal aorta (NAA). The diagnostic markers and immune cell infiltration of PVAT were further investigated by WGCNA, CIBERSORT, PPI, and multiple machine learning algorisms (including LASSO, RF, and SVM). Subsequently, eight-week-old C57BL/6 male mice ( = 10) were used to construct AAA models, and aorta samples were collected for molecular validation. Meanwhile, fifty-five peripheral venous blood samples from patients (AAA vs. normal: 40:15) in our hospital were used as an inhouse cohort to validate the diagnostic markers by qRT-PCR. The diagnostic efficacy of biomarkers was assessed by receiver operating characteristic (ROC) curve, area under the ROC (AUC), and concordance index (C-index).

Results: A total of 75 genes in the Grey60 module were identified by WGCNA. To select the genes most associated with PVAT in the grey60 module, three algorithms (including LASSO, RF, and SVM) and PPI were applied. and were identified as diagnostic markers of PVAT, with high accurate AUCs of 0.916, 0.926, and 0.948 (combined two markers). Additionally, the two biomarkers also displayed accurate diagnostic efficacy in the mice and inhouse cohorts, with AUCs and C-indexes all >0.8. Compared with the NAA group, PVAT around AAA was more abundant in multiple immune cell infiltration. Ultimately, the immune-related analysis revealed that and were associated with mast cells, T cells, and plasma cells.

Conclusion: and were diagnostic markers of PVAT around AAA and associated with multiple immune cells.
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http://dx.doi.org/10.3389/fcvm.2022.781207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8863960PMC
February 2022

Clinical Significance and Immune Landscape of a Pyroptosis-Derived LncRNA Signature for Glioblastoma.

Front Cell Dev Biol 2022 10;10:805291. Epub 2022 Feb 10.

Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Pyroptosis was recently implicated in the initiation and progression of tumors, including glioblastoma (GBM). This study aimed to explore the clinical significance of pyroptosis-related lncRNAs (PRLs) in GBM. Three independent cohorts were retrieved from the TCGA and CGGA databases. The consensus clustering and weighted gene coexpression network analysis (WGCNA) were applied to identify PRLs. The LASSO algorithm was employed to develop and validate a pyroptosis-related lncRNA signature (PRLS) in three independent cohorts. The molecular characteristics, clinical significances, tumor microenvironment, immune checkpoints profiles, and benefits of chemotherapy and immunotherapy regarding to PRLS were also explored. In the WGCNA framework, a key module that highly correlated with pyroptosis was extracted for identifying PRLs. Univariate Cox analysis further revealed the associations between PRLs and overall survival. Based on the expression profiles of PRLs, the PRLS was initially developed in TCGA cohort ( = 143) and then validated in two CGGA cohorts ( = 374). Multivariate Cox analysis demonstrated that our PRLS model was an independent risk factor. More importantly, this signature displayed a stable and accurate performance in predicting prognosis at 1, 3, and 5 years, with all AUCs above 0.7. The decision curve analysis also indicated that our signature had promising clinical application. In addition, patients with high PRLS score suggested a more abundant immune infiltration, higher expression of immune checkpoint genes, and better response to immunotherapy but worse to chemotherapy. A novel pyroptosis-related lncRNA signature with a robust performance was constructed and validated in multiple cohorts. This signature provided new perspectives for clinical management and precise treatments of GBM.
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http://dx.doi.org/10.3389/fcell.2022.805291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866949PMC
February 2022

The Efficacy of Drug-eluting Bead Transarterial Chemoembolization Loaded With Oxaliplatin for the Treatment of Stage III-IV Non-small-cell Lung Cancer.

Acad Radiol 2022 Feb 14. Epub 2022 Feb 14.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University. Electronic address:

Rationale And Objectives: To explore the safety and efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) loaded with oxaliplatin for stage III-IV non-small-cell lung cancer (NSCLC).

Materials And Methods: From October 2018 to May 2021, a total of 31 patients with stage III-IV NSCLC received DEB-TACE loaded with oxaliplatin. Demographic characteristics, adverse events (AEs), and treatment responses were collected. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method.

Results: All 31 patients successfully received DEB-TACE loaded with oxaliplatin. No procedure-related severe adverse events occurred. Hemoptysis symptoms presented in 8 patients but disappeared within 1-3 days. After DEB-TACE for 1, 2, and 6 months, the objective response rate (ORR) was 42%, 35%, and 26%, while the disease control rate (DCR) was 90%, 84% and 61%, respectively. The median PFS was 7 months (range 1-31 months), and the PFS rates at 3, 6, and 12 months were 87%, 71% and 29%, respectively. The median OS was 11 months (range 1-31 months), with OS rates of 87%, 77%, and 39% at 3, 6, and 12 months, respectively.

Conclusion: Oxaliplatin-loaded DEB-TACE is a feasible, safe, and effective treatment for patients with advanced refractory non-small-cell lung cancer.
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http://dx.doi.org/10.1016/j.acra.2022.01.015DOI Listing
February 2022

Stemness Refines the Classification of Colorectal Cancer With Stratified Prognosis, Multi-Omics Landscape, Potential Mechanisms, and Treatment Options.

Front Immunol 2022 27;13:828330. Epub 2022 Jan 27.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Stemness refers to the capacities of self-renewal and repopulation, which contributes to the progression, relapse, and drug resistance of colorectal cancer (CRC). Mounting evidence has established the links between cancer stemness and intratumoral heterogeneity across cancer. Currently, the intertumoral heterogeneity of cancer stemness remains elusive in CRC.

Methods: This study enrolled four CRC datasets, two immunotherapy datasets, and a clinical in-house cohort. Non-negative matrix factorization (NMF) was performed to decipher the heterogeneity of cancer stemness. Multiple machine learning algorithms were applied to develop a nine-gene stemness cluster predictor. The clinical outcomes, multi-omics landscape, potential mechanisms, and immune features of the stemness clusters were further explored.

Results: Based on 26 published stemness signatures derived by alternative approaches, we decipher two heterogeneous clusters, low stemness cluster 1 (C1) and high stemness cluster 2 (C2). C2 possessed a higher proportion of advanced tumors and displayed worse overall survival and relapse-free survival compared with C1. The MSI-H and CMS1 tumors tended to enrich in C1, and the mesenchymal subtype CMS4 was the prevalent subtype of C2. Subsequently, we developed a nine-gene stemness cluster predictor, which robustly validated and reproduced our stemness clusters in three independent datasets and an in-house cohort. C1 also displayed a generally superior mutational burden, and C2 possessed a higher burden of copy number deletion. Further investigations suggested that C1 enriched numerous proliferation-related biological processes and abundant immune infiltration, while C2 was significantly associated with mesenchyme development and differentiation. Given results derived from three algorithms and two immunotherapeutic cohorts, we observed C1 could benefit more from immunotherapy. For patients with C2, we constructed a ridge regression model and further identified nine latent therapeutic agents, which might improve their clinical outcomes.

Conclusions: This study proposed two stemness clusters with stratified prognosis, multi-omics landscape, potential mechanisms, and treatment options. Current work not only provided new insights into the heterogeneity of cancer stemness, but also shed light on optimizing decision-making in immunotherapy and chemotherapy.
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http://dx.doi.org/10.3389/fimmu.2022.828330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828967PMC
March 2022
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