Systemic assessment of manual circular stapler versus powered circular stapler for anastomosis in rectal cancer: A large-scale Chinese multicenter prospective cohort study.

Mechanical anastomosis in rectal cancer surgery offers several advantages but is plagued by complications like leaks and strictures. Variations in surgeons' experiences affect outcomes, but powered circular anastomosis has emerged as a promising solution, ensuring uniform staple formation and reducing manual manipulation. This multicenter, randomized, parallel-controlled study in China compared IntoCare™'s powered circular staplers (ICS) with manual circular staplers (MCS) in 382 patients (195 ICS, 187 MCS). Both groups had comparable anastomotic leakage rates. ICS significantly reduced anastomosis time while maintaining similar safety profiles. Postoperative recovery and complication rates were closely matched. The use of ICS in rectal cancer surgeries effectively reduces anastomosis time without compromising safety, offering a promising innovation to enhance the efficacy of rectal cancer surgeries while maintaining patient safety.

Personalized circulating tumor DNA monitoring improves recurrence surveillance and management after curative resection of colorectal liver metastases: a prospective cohort study.

BACKGROUND: Approximately 60% of patients with colorectal liver metastases (CRLM) experience relapse within 2 years after radical resection, previous studies have proven that repeat local treatment (LT) could prolong survival, however, it is difficult to seize the window for LT due to the lack of a high-sensitive surveillance method. In this study, the authors aim to examine the value of longitudinal circulating tumor DNA (ctDNA) in guiding adjuvant chemotherapy, optimizing clinical surveillance strategy, and thereby improving CRLM outcomes. MATERIALS AND METHODS: The authors conducted a prospective clinical trial using a personalized, tumor-informed ctDNA assay to monitor 60 CRLM patients undergoing resection with curative intent. Formalin-fixed paraffin-embedded tumor samples were collected after surgery. Blood samples were collected before surgery, 30 days after surgery (post-OP), and every third month until relapse or up to 2 years. RESULTS: A total of 394 plasma samples from 60 eligible patients were analyzed, with a median follow-up time of 31.3 months. Landmark analyses revealed that detectable ctDNA at post-OP (HR, 4.8), postadjuvant chemotherapy (HR, 6.0), and end-of-treatment (HR, 5.6) were associated with higher recurrence risk ( P <0.001). Post-OP ctDNA positivity served as the only independent prognostic marker in the multivariant analysis (HR, 5.1; P <0.001). Longitudinal ctDNA analysis identified relapsed patients at both sensitivity and specificity of 100%. Most (75%) patients were found with radiological relapse within 6 months after the first detectable ctDNA with a median lead time of 3.5 months. In relapsed patients, 73.2% had oligometastatic disease and 61% were liver-restricted, of which 72.0% received repeat LTs, and 60.0% achieved a secondary no evidence of disease status. CONCLUSIONS: Longitudinal ctDNA monitoring assists in early prediction of relapse, and thereby improves survival of CRLM patients by increased secondary resection rate and secondary no evidence of disease rate.

Performance and Solution Structures of Side-Chain-Bridged Oligo (Ethylene Glycol) Polymer Photocatalysts for Enhanced Hydrogen Evolution under Natural Light Illumination.

Converting solar energy into hydrogen energy using conjugated polymers (CP) is a promising solution to the energy crisis. Improving water solubility plays one of the critical factors in enhancing the hydrogen evolution rate (HER) of CP photocatalysts. In this study, a novel concept of incorporating hydrophilic side chains to connect the backbones of CPs to improve their HER is proposed. This concept is realized through the polymerization of carbazole units bridged with octane, ethylene glycol, and penta-(ethylene glycol) to form three new side-chain-braided (SCB) CPs: PCz2S-OCt, PCz2S-EG, and PCz2S-PEG. Verified through transient absorption spectra, the enhanced capability of PCz2S-PEG for ultrafast electron transfer and reduced recombination effects has been demonstrated. Small- and wide-angle X-ray scattering (SAXS/WAXS) analyses reveal that these three SCB-CPs form cross-linking networks with different mass fractal dimensions (f) in aqueous solution. With the lowest f value of 2.64 and improved water/polymer interfaces, PCz2S-PEG demonstrates the best HER, reaching up to 126.9 µmol h-1 in pure water-based photocatalytic solution. Moreover, PCz2S-PEG exhibits comparable performance in seawater-based photocatalytic solution under natural sunlight. In situ SAXS analysis further reveals nucleation-dominated generation of hydrogen nanoclusters with a size of ≈1.5 nm in the HER of PCz2S-PEG under light illumination.

An Autophagy-Associated MITF-GAS5-miR-23 Loop Attenuates Vascular Oxidative and Inflammatory Damage in Sepsis.

BACKGROUND: Sepsis induces GAS5 expression in the vascular endothelium, but the molecular mechanism is unclear, as is the role of GAS5 in sepsis. METHODS AND RESULTS: We observed that GAS5 expression in the endothelium was significantly upregulated in a sepsis mouse model. ChIP-PCR and EMSA confirmed that the oxidative stress (OS)-activated MiT-TFE transcription factor (MITF, TFE3, and TFEB)-mediated GAS5 transcription. In vitro, GAS5 overexpression attenuated OS and inflammation in endothelial cells (ECs) while maintaining the structural and functional integrity of mitochondria. In vivo, GAS5 reduced tissue ROS levels, maintained vascular barrier function to reduce leakage, and ultimately attenuated sepsis-induced lung injury. Luciferase reporter assays revealed that GAS5 protected MITF from degradation by sponging miR-23, thereby forming a positive feedback loop consisting of MITF, GAS5, and miR-23. Despite the fact that the OS-activated MITF-GAS5-miR-23 loop boosted MITF-mediated p62 transcription, ECs do not need to increase mitophagy to exert mitochondrial quality control since MITF-mediated Nrf2 transcription exists. Compared to mitophagy, MITF-transcribed p62 prefers to facilitate the autophagic degradation of Keap1 through a direct interaction, thereby relieving the inhibition of Nrf2 by Keap1, indicating that MITF can upregulate Nrf2 at both the transcriptional and posttranscriptional levels. Following this, ChIP-PCR demonstrated that Nrf2 can also transcribe MITF, revealing that there is a reciprocal positive regulatory association between MITF and Nrf2. CONCLUSION: In sepsis, the ROS-activated MITF-GAS5-miR-23 loop integrated the antioxidant and autophagy systems through MITF-mediated transcription of Nrf2 and p62, which dynamically regulate the level and type of autophagy, as well as exert antioxidant and anti-inflammatory effects.

Midterm Results of the Conservative, Bare Stent, and Bare Stent-Assisted Coiling Treatments for Symptomatic Isolated Superior Mesenteric Artery Dissection.

BACKGROUND: We compared the early and midterm (31, 3-63 months) outcomes of conservative treatment, bare stent treatment (BST), and bare stent-assisted coiling treatment (BSACT) to determine the most effective treatment for patients with symptomatic isolated superior mesenteric artery dissection (SISMAD). METHODS: Consecutive patients with SISMAD admitted to the study hospital between January 2016 and December 2021 were included in this retrospective study. Their demographic data, clinical findings, treatment options, early outcomes, and follow-up results were analyzed. RESULTS: A total of 121 patients were included in the study (23 with conservative treatment, 42 with BST, and 56 with BSACT). Symptoms were relieved in 91.3% of conservative patients, whereas all patients (100%) with BST or BSACT had symptom relief (P = 0.035). There was no significant difference in the length of hospital stay between the 2 endovascular treatments (P = 0.9051), but hospital stay was significantly shorter compared to conservative treatment (P < 0.0001). The cumulative rate of complete remodeling was 100% for BSACT versus 46.3% for BST (P < 0.0001) versus 42.9% for conservative patients (P < 0.0001). There were no significant differences between the last 2 groups (P = 0.3925). The prevalence of adverse events for abdominal pain recurrence and aneurysm formation was also significantly lower in the BSACT group at follow-up. CONCLUSIONS: BSACT for SISMAD has a preferable early outcome. The cumulative complete remodeling rate and the event-free survival rate are satisfactory at midterm follow-up. BSACT is an effective approach for SISMAD.

Early results of cyanoacrylate adhesive ablation versus laser ablation for the treatment of great saphenous vein insufficiency in the Chinese mainland population.

OBJECTIVE: In this study, we present our early outcomes of cyanoacrylate ablation (CA) versus endovenous laser ablation (EVLA) for the treatment of great saphenous vein (GSV) insufficiency in the Chinese mainland population. METHODS: We retrospectively analyzed 108 patients (53 patients in the CA group and 55 patients in the EVLA group) with GSV insufficiency who were treated with CA and EVLA between May 2020 and May 2021. The Venous Clinical Severity Score and Aberdeen Varicose Vein Questionnaire were used to assess clinical symptoms and quality of life, respectively. Total closure rates and procedure-related adverse events were also recorded in both groups. RESULTS: There was no significant difference between patients treated with CA or EVLA in terms of demographic and clinical characteristics. The average procedure time was 17 min in the CA group and 35 min in the EVLA group (p < 0.001). The CA group had lower pain scores during the procedure and 3 days afterward than the EVLA group (p < 0.001). At month 12, the CA group had a 90.4% closure rate, while the EVLA group had an 83.0% closure rate, with no significant difference between the two groups (p > 0.05). There was no significant difference in the Venous Clinical Severity Score or Aberdeen Varicose Vein Questionnaire score between the groups (p > 0.05). During follow-up, neither group experienced any significant adverse events, such as pulmonary embolism or deep venous thrombosis. The incidence of ecchymosis and paresthesia was significantly lower in the CA group than in the EVLA group (p < 0.05). CONCLUSIONS: Cyanoacrylate ablation has a high feasibility profile and is an effective approach to accomplish complete GSV target vein closure at early follow-up in the Chinese patients. Compared to EVLA, the improvement in quality-of-life outcomes is also sustained and similar, with less pain and fewer complications due to the absence of tumescence anesthesia and postprocedural compression stockings.

The pattern and treatment outcomes for rectal cancer with concurrent locoregional recurrence and distant metastases after total mesorectal excision.

BACKGROUND: To study the pattern and treatment outcome of rectal cancer (RC) with concurrent locoregional recurrence (LR) and distant metastasis (DM) after total mesorectal excision (TME) and to identify patient-, disease-, and treatment-related factors associated with differences in prognosis after concurrent LR and DM. METHODS: RC patients who were diagnosed with concurrent LR and DM after TME from May 2015 to June 2019 were included in our study. All patients received single or multiple treatment modalities under the guidance of multidisciplinary team (MDT) of colorectal cancer in Fudan University Shanghai Cancer Center. The prognostic value of various clinicopathological factors for survival were calculated by Kaplan-Meier curves and Cox regression analyses. RESULTS: A total of 74 RC patients with concurrent LR and DM who had undergone TME with a median follow-up of 27 months were eligible for analysis. The median survival of the included patients was 34 months, and 30 patients (41%) died. Fifty-nine patients (80%) underwent comprehensive treatments. Patients with oligometastatic disease (OMD) achieved no evidence of disease (NED) status more frequently than those with multiple metastases (P = 0.003). In the univariate analysis, patients achieving NED, diagnosed with OMD and five or less peritoneal metastases tended to have longer survival after LR and DM diagnosis (P < 0.05). In the multivariate analysis, attaining NED status was the only independent factor for survival (hazard ratio (HR), 2.419; P = 0.032). Survival after concurrent LR and DM in the non-NED group was significantly shorter than that in the NED group (median survival, 32 vs. 46 months; HR, 2.7; P = 0.014). CONCLUSIONS: The pattern and treatment outcome of RC with concurrent LR and DM after TME has changed with the development of multiple treatment modalities. Although the prognosis remains poor, pursuing NED status through comprehensive treatments may improve the survival of RC patients with concurrent LR and DM after TME.

Patient-Derived Organoids from Colorectal Cancer with Paired Liver Metastasis Reveal Tumor Heterogeneity and Predict Response to Chemotherapy.

There is no effective method to predict chemotherapy response and postoperative prognosis of colorectal cancer liver metastasis (CRLM) patients. Patient-derived organoid (PDO) has become an important preclinical model. Herein, a living biobank with 50 CRLM organoids derived from primary tumors and paired liver metastatic lesions is successfully constructed. CRLM PDOs from the multiomics levels (histopathology, genome, transcriptome and single-cell sequencing) are comprehensively analyzed and confirmed that this organoid platform for CRLM could capture intra- and interpatient heterogeneity. The chemosensitivity data in vitro reveal the potential value of clinical application for PDOs to predict chemotherapy response (FOLFOX or FOLFIRI) and clinical prognosis of CRLM patients. Taken together, CRLM PDOs can be utilized to deliver a potential application for personalized medicine.

Letter to the Editor: An ultra-sensitive assay using cell-free DNA fragmentomics for multi-cancer early detection.

Early detection can benefit cancer patients with more effective treatments and better prognosis, but existing early screening tests are limited, especially for multi-cancer detection. This study investigated the most prevalent and lethal cancer types, including primary liver cancer (PLC), colorectal adenocarcinoma (CRC), and lung adenocarcinoma (LUAD). Leveraging the emerging cell-free DNA (cfDNA) fragmentomics, we developed a robust machine learning model for multi-cancer early detection. 1,214 participants, including 381 PLC, 298 CRC, 292 LUAD patients, and 243 healthy volunteers, were enrolled. The majority of patients (N = 971) were at early stages (stage 0, N = 34; stage I, N = 799). The participants were randomly divided into a training cohort and a test cohort in a 1:1 ratio while maintaining the ratio for the major histology subtypes. An ensemble stacked machine learning approach was developed using multiple plasma cfDNA fragmentomic features. The model was trained solely in the training cohort and then evaluated in the test cohort. Our model showed an Area Under the Curve (AUC) of 0.983 for differentiating cancer patients from healthy individuals. At 95.0% specificity, the sensitivity of detecting all cancer reached 95.5%, while 100%, 94.6%, and 90.4% for PLC, CRC, and LUAD, individually. The cancer origin model demonstrated an overall 93.1% accuracy for predicting cancer origin in the test cohort (97.4%, 94.3%, and 85.6% for PLC, CRC, and LUAD, respectively). Our model sensitivity is consistently high for early-stage and small-size tumors. Furthermore, its detection and origin classification power remained superior when reducing sequencing depth to 1× (cancer detection: ≥ 91.5% sensitivity at 95.0% specificity; cancer origin: ≥ 91.6% accuracy). In conclusion, we have incorporated plasma cfDNA fragmentomics into the ensemble stacked model and established an ultrasensitive assay for multi-cancer early detection, shedding light on developing cancer early screening in clinical practice.

Circulating tumor DNA as a prognostic indicator of colorectal cancer recurrence-a systematic review and meta-analysis.

PURPOSE: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. After resection, patients need extensive follow-up to detect asymptomatic recurrences as early as possible to obtain optimal treatment. This study evaluated the prognostic value of circulating tumor DNA (ctDNA) for CRC recurrence. METHODS: Two investigators independently conducted a systematic literature search of peer-reviewed studies that investigated the prognostic value of ctDNA in CRC. Fixed effects or random effects models were applied for all analyses based on the assessment of heterogeneity. RESULTS: A total of 189 studies were initially retrieved from all databases; ultimately, eight studies with 879 CRC patients were included in this analysis. The pooled median recurrence-free survival was 11.36 months for ctDNA-positive patients. Meta-analysis of hazard ratio (HR) suggested that postoperative ctDNA-positive patients were more likely to experience cancer recurrence than ctDNA-negative patients (pooled HR: 5.41; 95% confidence interval (CI): 2.37-8.45). CONCLUSIONS: Successive monitoring of ctDNA status and follow-up with postoperative computed tomography (CT)/magnetic resonance imaging (MRI) are useful tools to detect early recurrence in postoperative ctDNA-positive patients.

Multi-dimensional fragmentomic assay for ultrasensitive early detection of colorectal advanced adenoma and adenocarcinoma.

Previous studies on liquid biopsy-based early detection of advanced colorectal adenoma (advCRA) or adenocarcinoma (CRC) were limited by low sensitivity. We performed a prospective study to establish an integrated model using fragmentomic profiles of plasma cell-free DNA (cfDNA) for accurately and cost-effectively detecting early-stage CRC and advCRA. The training cohort enrolled 310 participants, including 149 early-stage CRC patients, 46 advCRA patients and 115 healthy controls. Plasma cfDNA samples were prepared for whole-genome sequencing. An ensemble stacked model differentiating healthy controls from advCRA/early-stage CRC patients was trained using five machine learning models and five cfDNA fragmentomic features based on the training cohort. The model was subsequently validated using an independent test cohort (N = 311; including 149 early-stage CRC, 46 advCRA and 116 healthy controls). Our model showed an area under the curve (AUC) of 0.988 for differentiating advCRA/early-stage CRC patients from healthy individuals in an independent test cohort. The model performed even better for identifying early-stage CRC (AUC 0.990) compared to advCRA (AUC 0.982). At 94.8% specificity, the sensitivities for detecting advCRA and early-stage CRC reached 95.7% and 98.0% (0: 94.1%; I: 98.5%), respectively. Promisingly, the detection sensitivity has reached 100% and 97.6% in early-stage CRC patients with negative fecal occult or CEA blood test results, respectively. Finally, our model maintained promising performances (AUC: 0.982, 94.4% sensitivity at 94.8% specificity) even when sequencing depth was down-sampled to 1X. Our integrated predictive model demonstrated an unprecedented detection sensitivity for advCRA and early-stage CRC, shedding light on more accurate noninvasive CRC screening in clinical practice.

PUM1 Is Overexpressed in Colon Cancer Cells With Acquired Resistance to Cetuximab.

BACKGROUND: Cetuximab is an effective antibody to treat colorectal cancer (CRC) by targeting the epidermal growth factor receptor (EGFR). However, the mechanisms of acquired resistance to cetuximab therapy, especially in patients without identifiable gene mutations, are not fully understood. METHODS: Our study investigated the role of pumilio RNA-binding family member 1 (PUM1) in cetuximab resistance. We established cetuximab-resistant colon cancer cell lines SW480R and Caco-2R and knocked out PUM1 and DEAD-box helicase 5 (DDX5) with the clustered regularly interspaced short palindromic repeats (CRISPR)-caspase 9 (Cas9) system. To check cell proliferation, we used Cell Counting Kit-8. We performed qPCR and immunoblot to examine the levels of mRNAs and proteins for each cell line. RESULTS: Our data showed that PUM1 was upregulated in SW480R and Caco-2R cells with increased protein levels and cell proliferation, and PUM1 knockout reduced cell viability in the presence of cetuximab. We also found that PUM1 interacted with DDX5 in 3' untranslated region (UTR) and positively regulated its mRNA expression. Furthermore, suppression of DDX5 also decreased the proliferation of SW480R and Caco-2R cells. CONCLUSION: Our study suggests that PUM1 positively regulates DDX5 and acts as a promoter in cetuximab-resistant colon cancer cells.

Laparoscopic Transabdominal Preperitoneal Approach with Negative Pressure Drainage for Giant Inguinal Hernia.

Background: Giant inguinal hernia (GIH) is a rare disease but it can cause serious complications, such as intestinal obstruction and strangulation. Few studies have explored surgical treatment with respect to the transabdominal preperitoneal (TAPP) approach or measures to reduce the occurrence of postoperative seroma. Purpose: To investigate the safety and efficacy of the TAPP approach with negative pressure drainage in GIHs. Methods: From January 2017 to December 2019, 32 patients who underwent TAPP procedures with negative pressure drainage for GIHs at our hospital were reviewed. Demographic information, surgical characteristics, and follow-up data were obtained. Results: The mean age of the patients was 66, and more than half of them had medical comorbidities. All GIHs were defined as Type 1 and were successfully repaired through the TAPP approach with negative pressure drainage. The mean operative time was 146 minutes (range 122-251). After surgery, the mean drainage time was 7 days (range 5-10 days), and the mean volume of drainage in each patient was 820 mL (range 655-1020 mL). Complications occurred in 3 cases. For 1 case, the inferior epigastric artery was injured during surgery. A seroma was observed in 1 patient, which occurred 2 days after removal of the drainage tube. Finally, 1 patient developed an umbilical puncture site infection, and the wound healed after changing the dressing. The mean follow-up was 13 months (range 1-32), and there was no recurrence or mesh infection during that time. Conclusion: TAPP is a safe and effective approach for treating Type 1 GIHs with low operative complications. Negative pressure drainage through the scrotum to the preperitoneal space may reduce the incidence of seroma. Recurrence of hernias was not observed, and chronic pain seldom occurred during the follow-up period in our study.

Outcomes of Aspirex®S thrombectomy system combined with catheter-directed thrombolysis for treating bilateral lower extremity deep venous thrombosis.

BACKGROUND: Pharmacomechanical catheter-directed thrombolysis (PCDT) is rarely reported in treating bilateral lower extremity deep venous thrombosis (LEDVT). This study was aimed to investigate the safety, patency, and mid-term outcomes of the Aspirex®S thrombectomy system combined with catheter-directed thrombolysis (CDT) in treating symptomatic bilateral LEDVT. PATIENTS AND METHODS: The clinical data of 45 consecutive patients with acute or subacute bilateral LEDVT (60.00% male; mean age, 53.8 ± 16.5 years) who received endovascular treatment with PCDT between January 2015 and June 2019 were retrospectively analyzed in this study. The clinical efficacy of thrombolysis (≥50% thrombolysis), complications, primary patency, valvular function, and cumulative prevalence of post-thrombotic syndrome (PTS) were retrospectively analyzed. RESULTS: PCDT was performed in all 45 patients successfully. No serious procedure-related complication or death was observed. The average urokinase dosage was 4.1 ± 1.5 million IU, and the average thrombolysis time was 5.3 ± 1.3 days. The mean length of hospital stay was 9.9 ± 2.5 days. The primary patency was 100% after lysis. The clinical efficacy of thrombolysis was 86.7% (39/45). Deep venous thrombosis recurrence was observed in six (13.3%) patients within 12 months after discharge. The primary patency at 1-, 3-, 6-, 9-, and 12-month follow-up was 97.8%, 93.3%, 88.9%, 82.2%, and 73.3%, respectively. The cumulative prevalence of PTS was 24.4% (11/45) throughout the follow-up period, whereas the prevalence of moderate and severe PTS was only 6.7% (3/45). CONCLUSIONS: PCDT for treating bilateral LEDVT is feasible, effective, and safe.

Laparoscopic totally extraperitoneal (TEP) inguinal hernia repair in patients with liver cirrhosis accompanied by ascites.

To investigate the feasibility, efficacy, and safety of laparoscopic totally extraperitoneal (TEP) repair in patients with inguinal hernia accompanied by liver cirrhosis.Between October 2015 and May 2018, 17 patients with liver cirrhosis who underwent TEP repair were included in this study. The baseline characteristics, perioperative data, and recurrence were retrospectively reviewed.Seventeen patients with a mean duration of 18.23 ± 16.80 months were enrolled. All TEP repairs were successful without conversion to trans-abdominal pre-peritoneal (TAPP) surgery or open repair, but 4 patients had peritoneum rupture during dissection. The mean operation time was 54.23 ±â€Š10.51 minutes for unilateral hernia and 101.25 ±â€Š13.77 minutes for bilateral hernias. We found 2 cases with contralateral inguinal hernia and 2 cases with obturator hernia during surgery. The rate of complication was 17.65% (3/17), 2 of 3 cases were Child-Turcotte-Pugh C with large ascites. During a follow-up of 19.29 ±â€Š9.01 months, no patients had recurrence and chronic pain, but 2 patients died because of the progression of underlying liver disease.Early and elective inguinal hernia repair is feasible and effective for patients with liver cirrhosis. TEP is a feasible and safe repair option for cirrhotic patients in experienced hands.

Protective Role of RNA Helicase DEAD-Box Protein 5 in Smooth Muscle Cell Proliferation and Vascular Remodeling.

RATIONALE: RNA helicases, highly conserved enzymes, are currently believed to be not only involved in RNA modulation, but also in other biological processes. We recently reported that RNA helicase DDX (DEAD-box protein)-5 is required for maintaining the homeostasis of vascular smooth muscle cells (SMCs). However, the expression and function of RNA helicase in vascular physiology and disease is unknown. OBJECTIVE: To investigate the role of RNA helicase in vascular diseases. METHODS AND RESULTS: We showed here that DDX-5 was the most abundant DEAD-box protein expressed in human and rodent artery, which mainly located in SMCs. It was demonstrated that DDX-5 levels were reduced in cytokine-stimulated SMCs and vascular lesions. DDX-5 knocking down or deficiency increased SMC proliferation and migration, whereas overexpression of DDX-5 prevented aberrant proliferation and migration of SMCs. Mechanistic studies revealed transcription factor GATA (GATA-binding protein)-6 as a novel downstream target of DDX-5, which directly interacted with GATA-6 and protected it from MDM (mouse double minute)-2-mediated degradation. Our ChIP assay identified a previously unreported binding of p27Kip1 promoter to GATA-6. DDX-5 increased the recruitment of GATA-6 to p27Kip1 promoter, which enhanced p27Kip1 expression and maintained SMC quiescence. Finally, we showed exacerbated neointima formation in DDX-5 SMC-deficient mice after femoral artery injury, whereas overexpression of DDX-5 potently inhibited vascular remodeling in balloon-injured rat carotid artery. CONCLUSIONS: These findings provide the first evidence for a role of RNA helicase DDX-5 in the protection against SMC proliferation, migration, and neointimal hyperplasia. Our data extend the fundamental role of RNA helicase beyond RNA modulation, which provides the basic information for new therapeutic strategies for vascular diseases.

Platelet­derived growth factor D promotes the angiogenic capacity of endothelial progenitor cells.

Neovascularization and re-endothelialization rely on endothelial progenitor cells (EPCs). However, the recruitment and angiogenic roles of EPCs are subject to regulation through the vascular microenvironment, which remains largely unknown. Platelet­derived growth factor D (PDGF­D) is a new member of the PDGF family that binds the PDGFR­ß homodimer. However, it remains unknown whether and how it affects the angiogenic capacity of EPCs and participates in tube­like formation. EPCs were derived from rat bone marrow cells, and the gain­of­function approach was used to study the effects of PDGF­D on the biological activities of EPCs. EPCs that stably express PDGF­D were generated by lentiviral­mediated transduction, and the expression levels were evaluated by western blotting and reverse transcription, followed by real­time quantitative polymerase chain reaction (RT­qPCR). The biological activities of EPCs evaluated in the present study included proliferation, adhesion, migration, tube formation and senescence. Furthermore, the downstream signaling of PDGF­D was explored by western blot analysis. The results revealed that the lentiviral­mediated expression of PDGF­D in the microenvironment promoted the migration, proliferation, adhesion and tube formation of EPCs. In addition, PDGF­D suppressed the senescence of EPCs. Mechanistically, PDGF­D induced the phosphorylation of several signaling molecules, including STAT3, AKT, ERK1/2, mTOR and GSK­3ß, suggesting that PDGF­D enhanced the angiogenic function of EPCs through PDGF receptor­dependent and ­independent signaling pathways. In conclusion, PDGF­D promotes the angiogenic capacity of EPCs, including proliferation, migration, adhesion and tube formation, and thereby contributes to angiogenesis.

Catheter-directed thrombolysis through anterior tibial vein for treating acute extensive deep venous thrombosis.

OBJECTIVE: The objective of this study was to evaluate the feasibility, efficacy, and safety of catheter-directed thrombolysis (CDT) through an anterior tibial vein approach for acute extensive lower extremity deep venous thrombosis (DVT). METHODS: There were 125 consecutive patients with acute extensive lower extremity DVT who received CDT through an anterior tibial vein approach between October 2014 and June 2017. The patients with iliac vein compression syndrome were treated with balloon dilation and stent implantation after CDT. The thrombus score differences, limb circumference differences, venous patency, and complications were retrospectively analyzed. RESULTS: The anterior tibial vein approach was successfully achieved in 118 patients (94.40% [118/125]). The mean thrombolysis time was 5.28 ± 1.10 days, and the average dose of urokinase was 3,903,400 ± 766,900 IU. Metal stents were placed in 50 patients (42.37% [50/118]). There were 109 patients (92.37% [109/118]) who had successful lysis (grade II and grade III lysis); 31 patients (91.18% [31/34]) achieved grade III lysis (no residual thrombus) within 3 days of symptom onset. In contrast, only 33.96% (18/53) of those treated within 4 to 7 days and 9.68% (3/31) of those treated after 7 days achieved grade III lysis. Compared with findings before CDT, the limb circumference above and below the knee was significantly reduced (7.22 ± 2.54 cm vs 1.58 ± 0.75 cm and 5.14 ± 1.41 cm vs 1.19 ± 0.49 cm, respectively). The incidence of bleeding was 10.17% (12/118). Six patients had puncture site bleeding, and three patients suffered major bleeding. One puncture site infection and two catheter-directed infections were observed during treatment. Two patients had accidental anterior tibial artery injury and recovered without complications, and no nerve injury occurred. During a follow-up of 19.39 ± 7.47 months (6-32 months), femoral venous insufficiency and popliteal venous insufficiency were present in 21.65% (21/97) and 30.93% (30/97) of the patients. The overall patency and post-thrombotic syndrome rates were 83.51% (81/97) and 21.65% (21/97). CONCLUSIONS: CDT through an anterior tibial vein approach is a feasible, effective, and safe method for acute extensive lower extremity DVT patients. In addition, the anterior tibial vein approach can be an alternative to the traditional CDT approach.

A Retrospective Study Comparing 2 Approaches to Catheter-Directed Thrombolysis for Acute Deep Venous Thrombosis.

BACKGROUND: To compare the clinical efficacy and safety of catheter-directed thrombolysis (CDT) using the anterior tibial vein approach (ATVA) and popliteal vein approach (PVA) for acute lower-extremity deep venous thrombosis (LEDVT). METHODS: From March 2014 to October 2015, 63 patients with unilateral acute extensive LEDVT were enrolled in this study: 36 patients received CDT via the PVA group, and 27 patients received CDT via the ATVA group. Limb circumference, thrombus score, complications, thrombolytic time, and the amount of thrombolytic agents administered were recorded. Postthrombotic syndrome (PTS) and venous insufficiency were assessed at 1 year after treatment. RESULTS: Thrombus scores were significantly decreased in both groups after CDT therapy (each P < 0.001). There was no significant difference in the detumescence and thrombolytic rates, thrombolytic times and administered amounts of thrombolytic agents between the 2 groups (each P > 0.050). The limb circumference difference below the knee in the ATVA group was lower than that in the PVA group (P = 0.029), and the ATVA resulted in fewer complications, especially sheath bleeding (P = 0.025). At the 1-year follow-up, popliteal venous insufficiency was present in 36.11% of the PVA group and 25.93% of the ATVA group (P = 0.390). In addition, PTS was observed in 13.89% of the PVA group compared with 7.41% of the ATVA group (P = 0.268). CONCLUSIONS: CDT is an effective and safe method for treating acute LEDVT. The ATVA is an effective and feasible approach for CDT with a lower incidence of complications than the PVA.