Directional atherectomy and drug-coated balloon angioplasty vs. bare nitinol stent angioplasty for femoropopliteal artery lesions.

Background: The present study evaluated the prognosis of directional atherectomy (DA)+drug-coated balloon (DCB) angioplasty for femoropopliteal artery lesions compared with bare nitinol stent (BNS). Patients and methods: This retrospective cohort study included patients with femoropopliteal artery lesions who underwent percutaneous endovascular surgery between January 2016 and June 2019. The primary outcome was the primary patency rate after 12, 24, and 36 months; the secondary outcomes comprised incidence of flow-limiting dissections, technical success, limb salvage, and all-cause death. Results: During the study period, 110 (44%) patients underwent DA+DCB, and 140 (56%) patients underwent bare nitinol stent (BNS). There were no differences in the 12- and 24-month patency rates of the two groups (98.2% vs. 93.6% and 68.2% vs. 60.0%, both p>.05). The 36-month primary patency rate in the DA+DCB group was significantly higher than that of the BNS group (27.3% vs. 15.7%, p=.003). The technical success rate and all-cause death were similar between groups (p>.05). Flow-limiting dissections occurred more frequently in the BNS group than in the DA+DCB group (27.9% vs. 10.9%, p=.033). After adjustment for potential confounders, such as sex, smoking, hypertension, hyperlipidemia, ABI after surgery, TASC II B, lesion length ≥15 cm, two-vessel runoff, and three-vessel runoff, the HR for primary patency rate comparing BNS to DA+DCB was 2.61 (95%CI: 1.61-4.25). Conclusions: In this retrospective cohort study, DA+DCB was associated with a higher 30-month primary patency rate and a lower flow-limiting dissection incidence than BNS.

A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Hepatocyte Growth Factor in the Treatment of Critical Limb Ischemia.

NL003 is a plasmid engineered to simultaneously express two isoforms of hepatocyte growth factor. This phase II study was performed to assess the clinical safety and efficacy of intramuscular injection of NL003 in critical limb ischemia (CLI) patients for 6 months. Two hundred patients (Rutherford scale 4-5) were randomly assigned: placebo (n = 50), low-dose NL003 (n = 50), middle-dose NL003 (n = 50), or high-dose NL003 (n = 50). The drug was administered in the affected limb of 197 patients on days 0, 14, and 28. No significant differences in the incidence of adverse events (AEs) or serious AEs were found among the groups. At 6 months, pain severity was significantly reduced in all NL003 groups, but not in the placebo group (p < 0.05). The proportion of patients with complete ulcer healing in the high-dose group was significantly higher than that of the placebo group (p = 0.0095). There were no statistically significant differences in transcutaneous oxygen pressure (TcPO2), ankle-brachial index (ABI), or toe-brachial index (TBI) value among the four groups throughout the study period. These results provide the first effective evidence of significant improvements in total healing of ulcers in treated legs, complete pain relief without analgesics, and safety for NL003 in patients with Rutherford stage 4-5.

Midterm Outcome of Directional Atherectomy Combined with Drug-Coated Balloon Angioplasty Versus Drug-Coated Balloon Angioplasty Alone for Femoropopliteal Arteriosclerosis Obliterans.

BACKGROUND: The "leave nothing behind" strategies have been becoming a popular treatment for femoropopliteal arteriosclerosis obliterans. Atherectomy before drug-coated balloon (DCB) angioplasty may have an advantage in improving the efficiency of drug delivery into the blood vessel wall. This study aimed to compare the therapeutic effects of directional atherectomy combined with DCB angioplasty with DCB angioplasty alone in the treatment of femoropopliteal arteriosclerosis obliterans. METHODS: Patients with femoropopliteal arteriosclerosis obliterans who received endovascular therapy from June 2016 to June 2018 in our hospital and presented with life-limiting claudication or severe chronic limb ischemia comprised the study cohort. The patients were randomized to receive directional atherectomy combined with DCB angioplasty (n = 45) or DCB alone (n = 49). Ninety-four patients were enrolled in our study with 72 males, and the mean age was 67 ± 10 years. The mean lesion length was 112 ± 64 mm. RESULTS: There were no significant differences in the baseline characteristics of patients and lesions between the 2 randomized groups (P > 0.05). Flow-limiting dissections occurred more frequently in the DCB group (n = 12; 24.5%) than in the DA-DCB group (n = 2; 4.4%; P = 0.006). The technical success rate in the DA-DCB group was superior to that in the DCB group (95.6% vs. 75.5%, P = 0.006). The mean follow-up duration was 16.7 ± 6.1 months in the DCB group and 15.3 ± 5.8 months in the DA-DCB group. No amputations were performed. The overall mortality in the DCB group was 4.1% (2/49), while all patients survived in the DA-DCB group. The 12-month and 24-month primary patencies in the DA-DCB group were greater than those in the DCB group (80.5% vs. 75.7% and 67.1% vs. 55.1%, respectively); however, using all available patency data, no significant differences over time were observed (P = 0.377). CONCLUSIONS: In this study, directional atherectomy combined with DCB angioplasty can decrease the flow-limiting dissection rate in the treatment of femoropopliteal arteriosclerosis obliterans compared with DCB angioplasty alone. There was no significant difference between the 2 groups in terms of primary patency rate which was needed to be further clarified.

Endovascular repair of subclavian artery aneurysms: results from a single-center experience.

OBJECTIVE: To present our experience of the endovascular treatment of subclavian artery aneurysms (SAAs) and analyze the clinical manifestations, imaging findings and treatment outcomes. METHODS: In this retrospective study, nine patients with SAAs underwent endovascular stent placement in our center between July 2011 and June 2016. Clinical features, imaging findings, treatment outcomes and follow-up results of these SAA patients were retrospectively analyzed. RESULTS: Nine patients were diagnosed with SAAs by computer tomography angiography (CTA). Five patients underwent percutaneous endovascular stent placement in the subclavian artery. Three patients underwent endovascular repair of the SAAs with coil embolization and stent graft. One patient underwent stent graft implantation by the simultaneous kissing stent technique. Five patients had their symptoms relieved and thrombosis occurred in one case. The mean follow-up period was 17 months, ranging from 8 to 40 months. CONCLUSION: For patients with SAAs, endovascular treatment is a feasible choice, with a high success rate, few complications and good clinical outcomes.

Crosstalk between TGF-ß/Smad3 and BMP/BMPR2 signaling pathways via miR-17-92 cluster in carotid artery restenosis.

In the recent decades, carotid angioplasty and stenting (CAS) has been developed into a credible option for the patients with carotid stenosis. However, restenosis remains a severe and unsolved issue after CAS treatment. Restenosis is characterized by neointimal hyperplasia, which is partially caused by vascular smooth muscle cells (VSMC) proliferation. However, the molecular mechanism involved in the restenosis is still unclear. In this study, we demonstrated a functional crosstalk between two TGF-ß superfamily signaling pathway members, Smad3 and BMPR2, in VSMC proliferation. Smad3 plays an important role in the TGF-ß/Smad3 signaling pathway, and is significantly upregulated in the carotid artery with restenosis to promote VSMC proliferation. In contrast, BMP receptor II (BMPR2), an inhibitor of VSMC proliferation is downregulated in carotid restenosis. We further found that BMPR2 downregulation is mediated by miR-17-92 cluster, which is transcriptionally regulated by Smad3. Thus, Smad3 upregulation and Smad3/miR-17-92 cluster-dependent BMPR2 downregulation are likely to promote VSMC proliferation and restenosis. Taken together, our results may provide novel clues for early diagnosis of carotid restenosis and developing new therapeutic strategy.

Stent Insertion for Inoperable Hilar Cholangiocarcinoma: Comparison Between Unilateral Radioactive Stent and Bilateral Normal Stent.

OBJECTIVE: To comparatively analyze the clinical efficacy and safety of unilateral radioactive stent (RS) insertion versus bilateral normal stent (NS) insertion in patients with inoperable hilar cholangiocarcinoma (HC). PATIENTS AND METHODS: Patients with inoperable HC were treated in our hospital from January 2016 to December 2020. The treatment approach included the insertion of either unilateral RS or bilateral NS, evaluating the efficacy and safety of therapy in 2 distinct groups. RESULTS: A total of 58 individuals experienced the insertion of a unilateral RS, whereas 57 patients underwent the insertion of bilateral NS. No statistically significant difference between the unilateral RS and bilateral NS groups was seen in the technical success rates (98.3% vs 94.7%, P = 0.598) and clinical success rates (98.2% vs 100%, P = 0.514). While there is no statistically significant difference in the rates of stent restenosis (19.3% vs 9.3%, P = 0.132) between the two groups, the unilateral RS group demonstrated substantially longer stent patency (202 vs 119 d, P = 0.016) and overall survival (229 vs 122 d, P = 0.004) compared with the bilateral NS group. Moreover, 8 patients (14.0%) in the unilateral RS group and 14 patients (25.9%) in the bilateral NS group had postoperative complications with no significant difference ( P = 0.116). CONCLUSION: When inserting stents for inoperable HC, both unilateral RS and bilateral NS insertion procedures have demonstrated favorable therapeutic efficacy. Nevertheless, inserting a unilateral RS provided a longer duration of stent patency and overall survival than implantation of bilateral NS.

[Clinical Efficacy Analysis of Wedge Resection of Pulmonary 
in Patients with Small Volume Invasive Lung Adenocarcinoma].

BACKGROUND: With further understanding and research into non-small cell lung cancer with tumours ≤2 cm in maximum diameter, segmental lung resection is able to achieve the same long-term prognosis as lobectomy. However, there are few studies on the prognostic effect of wedge resection on small volume invasive lung adenocarcinoma with an invasion depth of 0.5 to 1.0 cm. Therefore, this study focuses on the clinical efficacy and prognosis of wedge resection in patients with small-volume invasive lung adenocarcinoma. METHODS: A retrospective analysis of the medical records of 208 patients who underwent surgery in the Department of Thoracic Surgery of the Affiliated Provincial Hospital of Anhui Medical University from February 2016 to December 2017 was made, and the postoperative pathological results confirmed small volume invasive lung adenocarcinoma. According to their surgical methods, they were divided into lobectomy group (n=115), segmentectomy group (n=48) and wedge resection group (n=45). Kaplan-Meier survival curve estimation and Cox proportional risk regression model were used to explore the influence of different surgical methods on the prognosis of patients with small volume invasive lung adenocarcinoma. RESULTS: The wedge resection group had better perioperative outcomes compared with the segmentectomy group and lobectomy group, with statistically significant differences in intraoperative bleeding (P=0.036), postoperative drainage (P<0.001), operative time (P=0.018), postoperative time with tubes (P=0.001), and postoperative complication rate (P=0.006). There were no significant differences when comparing the three groups in terms of survival rate (lobectomy group vs segmentectomy group, P=0.303; lobectomy group vs wedge resection group, P=0.742; and segmentectomy group vs wedge resection group, P=0.278) and recurrence-free survival rate (lobectomy group vs segmentectomy group, P=0.495; lobectomy group vs wedge resection group, P=0.362; segmentectomy group vs wedge resection group, P=0.775). Univariate and multivariate survival analyses showed that consolidation tumor ratio (CTR) was the prognostic factor of overall survival and revurrence-free survival for patients with small-volume invasive lung adenocarcinoma (P<0.05). CONCLUSIONS: Wedge resection in patients with small volume invasive lung adenocarcinoma can achieve long-term outcomes similar to segmentectomy and lobectomy. When the CTR≤0.5, wedge resection is preferred in such patients.

In vivo evaluation of safety and performance of a tapered nitinol venous stent with inclined proximal end in an ovine iliac venous model.

A tapered stent with inclined proximal end is designed for fitting the iliac anatomically. The aim of the present study was to evaluate the safety and performance of the new stent in ovine left iliac veins. The experiment was performed in 30 adult sheep, and one nitinol-based VENA-BT® iliac venous stent (KYD stent) was implanted into each animal's left common iliac vein. Follow-up in all sheep consisted of angiographic, macroscopic, and microscopic examinations at Day 0 (< 24 h), Day 30, Day 90, Day 180 and Day 360 post-stenting (six animals per each time-point). 30 healthy ~ 50 kg sheep were included in this study and randomly divided into five groups according to the follow-up timepoint. All stents were implanted successfully into the left ovine common iliac vein. No significant migration occurred at follow-up. There is no statistically significant difference between the groups (p > 0.05), indicating no serious lumen loss occurred during the follow-up period. Common iliac venous pressure was further measured and the results further indicated the lumen patency at follow-up. Histological examinations indicated that no vessel injury and wall rupture, stent damage, and luminal thrombus occurred. There was moderate inflammatory cell infiltration around the stent in Day-0 and Day-30 groups with the average inflammation score of 2.278 and 2.167, respectively. The inflammatory reaction was significantly reduced in Day-90, Day-180 and Day-360 groups and the average inflammation scores were 0.9444 (p < 0.001, Day-90 vs Day-0), 1.167 (p < 0.001, Day-180 vs Day-0) and 0.667 (p < 0.001, Day-90 vs Day-0), respectively. The microscopic examinations found that the stents were well covered by endothelial cells in all follow-up time points. The results suggested that the KYD stent is feasible and safe in animal model. Future clinical studies may be required to further evaluate its safety and efficacy.

Uhrf2 is important for DNA damage response in vascular smooth muscle cells.

Emerging evidence shows that Uhrf1 plays an important role in DNA damage response for maintaining genomic stability. Interestingly, Uhrf1 has a paralog Uhrf2 in mammals. Uhrf1 and Uhrf2 share similar domain architectures. However, the role of Uhrf2 in DNA damage response has not been studied yet. During the analysis of the expression level of Uhrf2 in different tissues, we found that Uhrf2 is highly expressed in aorta and aortic vascular smooth muscle cells. Thus, we studied the role of Uhrf2 in DNA damage response in aortic vascular smooth muscle cells. Using laser microirradiation, we found that like Uhrf1, Uhrf2 was recruited to the sites of DNA damage. We dissected the functional domains of Uhrf2 and found that the TTD, PHD and SRA domains are important for the relocation of Uhrf2 to the sites of DNA damage. Moreover, depletion of Uhrf2 suppressed DNA damage-induced H2AX phosphorylation and DNA damage repair. Taken together, our results demonstrate the function of Uhrf2 in DNA damage response.

Debulking plus drug-coated balloon angioplasty versus drug-coated balloon angioplasty alone for femoropopliteal Tosaka III in-stent restenosis lesions.

Introduction: Femoropopliteal (FP) Tosaka class III in-stent restenosis (ISR) lesions remain a significant clinical problem and optimal revascularization management including the use of drug-coated balloon (DCB) and debulking devices has the potential to improve the outcomes for these patients. Aim: To compare clinical outcomes of debulking plus DCB with DCB alone in Tosaka III FP-ISR treatment in a Chinese population. Material and methods: This was a single-center retrospective study of patients who underwent endovascular interventions of debulking plus DCB or DCB alone for Tosaka III FP-ISR lesions. One-year primary patency was the main outcome. Other outcome measures are 12-month freedom from clinical-driven target lesion revascularization (f-CD-TLR), technical success rate, and periprocedural complications. Results: A total of 80 patients with Tosaka III FP-ISR were included; 39 were treated with debulking plus DCB, among whom 22 were treated with laser atherectomy (LA) plus DCB and 17 were treated with rotational atherectomy (RA) plus DCB. 41 were treated with DCB alone. 12-month primary patency was significantly different between the debulking + DCB and DCB groups (87.2% vs. 65.9%, p = 0.039). in the subgroup comparison, no significant difference was found between the LA + DCB and RA + DCB groups (86.4% vs. 88.2%, p = 0.842). There were also no significant differences in the group and subgroup comparison of 12-month f-CD-TLR, technical success rate, and periprocedural complications. Conclusions: In this small preliminary experience, combined treatment with debulking and DCB angioplasty is correlated with better outcomes in 1-year primary patency for Tosaka III FP-ISR lesions.

Outcomes of covered stents versus bare-metal stents for subclavian artery occlusive disease.

Objective: To compare the clinical efficacy of covered stents and bare-metal stents in the endovascular treatment of subclavian artery occlusive disease. Methods: Between January 2014 and December 2020, 161 patients (112 males) underwent stenting of left subclavian arteries; CSs were implanted in 55 patients (34.2%) and BMSs in 106 (65.8%). Thirty-day outcomes, mid-term patency, and follow-up results were analyzed with Kaplan-Meier curves. Relevant clinical, anatomical, and procedural factors were evaluated for their association with patency in the two groups using Cox proportional hazards regression. Results: Mean follow-up was 45 ± 18 months. The primary patency was 93.8% (95% CI, 81.9%-98.0%) in the covered stent group and 73.7% (95% CI, 63.2%-81.6%; P = 0.010) in the bare-metal stent group. The primary patency in the total occlusion subcategory was significant in favor of CS (93.3%, 95% CI, 61.26%-99.0%) compared with BMS (42.3%, 95% CI, 22.9%-60.5%; P = 0.005). Cox proportional hazards regression indicated that the use of BMSs [hazard ratio (HR), 4.90; 95% CI, 1.47-16.31; P = 0.010] and total occlusive lesions (HR, 7.03; 95% CI, 3.02-16.34; P < 0.001) were negative predictors of patency, and the vessel diameter (HR, 3.17; 95% CI, 1.04-9.71; P = 0.043)) was a positive predictor of patency. Conclusion: Compared with bare stents, covered stents have a higher midterm primary patency in the treatment of subclavian artery occlusive disease.

[Management strategies of arterial prosthetic graft infection in lower extremity:a report of 5 cases].

OBJECTIVE: To explore the management strategies of pyogenic vascular prosthetic graft infection. METHODS: The clinical data of 5 cases of prosthetic vascular graft infection in lower extremity between 2003 and 2010 were retrospectively analyzed. RESULTS: All of them were treated by antibiotics, debridement and drainage. One patient died from acute myocardial infarction and septic shock. Two patients were cured by extra-anatomic arterial bypass and removal of infected graft after a basic control of infections. And another two patients had the diseased limb amputated after the removal of infected vascular graft without blood reconstruction. CONCLUSION: Pyogenic infection of vascular graft is hard to treat with conservative measures. Revascularization prior to removal of infected graft is recommended for a better outcome.

A phase I clinical study of naked DNA expressing two isoforms of hepatocyte growth factor to treat patients with critical limb ischemia.

BACKGROUND: The purpose of the present phase I clinical trial was to evaluate the safety, tolerability, and preliminary efficacy of naked DNA therapy expressing two isoforms of hepatocyte growth factor (pCK-HGF-X7) in critical limb ischemia (CLI) patients. MATERIALS AND METHODS: Twenty-one patients with CLI were consecutively assigned to receive increasing doses (cohort I: 4 mg; cohort II: 8 mg; cohort III: 12 mg; and cohort IV: 16 mg) of pCK-HGF-X7, which was administered into the ischemic calf and/or thigh muscle at days 1 and 15. A safety and tolerability evaluation and measurement of pain severity score using a visual analog scale (VAS), ulcer status, transcutaneous oxygen (TcPO(2) ) and ankle-brachial index (ABI) were performed throughout a 3-month follow-up period. RESULTS: No serious adverse events were observed in any of the 21 patients for the 3-month follow-up period. A significant reduction in pain was observed in the treated patients, with the mean VAS decreasing from 5.95-1.64 (p < 0.001). The mean ABI value increased from 0.49-0.63 (p = 0.026) at 3-month follow-up. The mean TcPO(2) value on the dorsum of the foot, the anterior calf and posterior calf significantly increased from 28.25-39.28 mmHg (p = 0.012), from 22.00-30.63 mmHg (p = 0.046) and 32.05-47.19 mmHg (p = 0.001) at 3-month follow-up, respectively. Wound healing improvement was observed in the six of nine patients that had an ulcer at baseline. CONCLUSIONS: These results support the performance of a phase II randomized controlled trial with pCK-HGF-X7.

[Efficacies of carotid endarterectomy in the treatment of atherosclerotic carotid artery stenosis].

OBJECTIVE: To explore the feasibility and efficacy of carotid endarterectomy (CEA) in the treatment of atherosclerotic carotid artery stenosis (ACAS). METHODS: From January 2002 to December 2010, 126 ACAS patients undergoing carotid endarterectomy at our hospital were retrospectively analyzed. There were 92 males and 34 females with an average age of 65.5 years old (range: 48 - 75). Among them, 25 had sequelae of cerebral infarction, 69 symptomatic cerebral ischemia and 32 asymptomatic. Sixty-two patients were monitored intra-operatively with transcranial Doppler (TCD). Among them, 5 patients underwent arterial shunt due to a reduced of blood flow in middle cerebral artery for over 50%. The other 64 patients without TCD monitoring underwent intra-operative arterial shunt. And 22 patients underwent patch angioplasty with autologous or prosthetic vascular patch. Intracranial hyperperfusion was prevented by a compression of common carotid artery or control was successful without perioperative mortality. All patients with cerebral ischemic symptoms and some patients with cerebral infarction sequelae had much post-operative improvement. Deviated tongue protrusion occurred in 10 patients and 8 of them recovered at Week 2 post-operation. And 118 patients were followed up for a mean period of 46.5 months (range: 6 - 96). Two patients with deviated tongue protrusion had slight improvements; 2 patients with severe carotid artery stenosis underwent stent angioplasty; 4 patients with moderate carotid artery stenosis received conservative treatment; among 7 deceased patients, two died of cerebral infarction. CONCLUSION: CEA is effective in the treatment of carotid artery stenosis with a high success rate. TCD monitoring during CEA is valuable for preventing cerebral ischemia and intracranial hyperperfusion. Arterial shunt and arterial patch angioplasty should be considered according to certain conditions during CEA.

Intravascular Guidewire Residue After Endovascular Embolization for Intractable Epistaxis: A Case Report.

Endovascular embolization (EE) has become an effective method for the treatment of intractable epistaxis (IE). However, complications such as facial pain, headaches, aphasia, hemiplegia, and transient blindness can also occur during or after surgery. In this article, we report a rare case of IE with residual intravascular guidewire after EE. Open surgery was used to remove the guidewire. However, to avoid serious complications such as massive hemorrhage, only part of the guidewire was removed.

A Retrospective Comparative Study of Twelve-Month Clinical Outcomes for Drug-Coating Balloon Angioplasty and Stent Implantation in Treating Patients with Popliteal Obstructive Lesions.

PURPOSE: Despite increased interest in treating superficial femoral and popliteal arteries with endovascular technology, there is little data regarding comparative results of different treatment modalities in the popliteal artery. It was hypothesized that to improve clinical outcomes in this segment, drug-coating balloon (DCB) angioplasty would not be inferior to stent implantation. METHODS: The records of consecutive Chinese patients with popliteal lesions who were treated with DCB or stenting between June 2016 and February 2017 were retrospectively reviewed. The preoperative demographic, lesion characteristics and postoperative outcomes were compared and statistically analyzed. All patients were divided into different subgroups according to the degree of calcium or degree of ischemia. RESULTS: One hundred two consecutive patients with popliteal lesions were treated with DCB or stenting and 95 (93.1%) completed a follow-up. Critical limb ischemia was present in 70.5% and occlusions were present in 61.1% of patients. DCB angioplasty was performed on 43 patients and angioplasty with primary stenting was performed on 52 patients. There was no difference in twelve-month primary patency (79.1% vs 82.7%; P = 0.687), secondary patency (95.3% vs 94.2%; P = 0.808) and amputation-free survival (93.0% vs 94.2%; P = 0.825) between the DCB group and stent groups. In patients with severe calcium, the twelve-month primary patency (61.1% vs. 79.2%; P = 0.239) and amputation-free survival (83.3% vs 87.5%; P = 0.739) did not differ between the DCB and stent groups. CONCLUSIONS: This study demonstrates that DCB treatment in Chinese patients with popliteal atherosclerotic occlusive lesions can be associated with similar twelve-month patency and amputation-free survival compared to stenting, even in patients with severe calcification. LEVEL OF EVIDENCE: Level 3a, Non-randomized follow-up study.

Phenotypic Switching of Atherosclerotic Smooth Muscle Cells is Regulated by Activated PARP1-Dependent TET1 Expression.

AIM: During the development of atherosclerosis, the vascular smooth muscle cells (SMCs) undergo phenotypic switching from contractile phenotype to synthetic phenotype. This study aimed at examining the role of DNA modification mediated by the oxidative stress dependent ten eleven translocation enzymes (TETs) expression at early stage of phenotypic switching. METHODS: Based on the in vitro SMCs calcification model, DNA damage, phenotypic switching and 5-hydroxymethylcytosine (5hmC) were examined by comet assay, alkaline DNA unwinding assay, immunofluorescence staining, Dot blotting and Western blotting. Then Western blotting and qRT-PCR were performed to analyze the TETs expression and the relationship between the activity of poly(ADP-ribose) polymerase 1 (PARP1) and TETs expression. We further alter 5hmC modification by inhibition of TET1 or PARP1 to rescue the phenotypic switching of SMCs using immunofluorescence staining, Dot blotting and qRT-PCR. We performed immunochemistry staining to examine the activated PARP1-TET1 pathway in vivo. RESULTS: The phenotypic switching was observed in the SMCs cultured with calcification medium as the expression of the cell markers of contractile SMCs decreased and cell proliferation increased. In contrast, PAR and 5hmC were markedly increased in SMCs with calcification due to DNA damage. Our study further demonstrated that oxidative stress-activated PARP1, promotes TET1 expression and 5hmC increase during the phenotypic switching. Inhibition of TET1 or PARP1 can rescue the phenotypic switching of SMCs with calcification. CONCLUSION: Our study demonstrated the important role of PARylation dependent 5hmC, in SMCs phenotypic switching. It raises the possibility to target TET1 and PARP1 for atherosclerosis treatment.

pUDK-HGF Gene Therapy to Relieve CLI Rest Pain and Ulcer: A Phase II, Double-Blind, Randomized Placebo-Controlled Trial.

This phase II clinical trial investigated the efficacy and safety of intramuscular injection of plasmid pUDK-HGF, which encodes the human hepatocyte growth factor gene in patients with critical limb ischemia. Resting pain patients (n = 119) and patients with leg ulcers (n = 121) were enrolled as two cohorts and randomized to receive pUDK-HGF treatment on days 0, 14, and 28. In the resting pain cohort, the proportion of patients with complete pain relief on day 180 after receiving pUDK-HGF injection, as the primary outcome, was significantly higher than that of the placebo group on the same day (p = 0.0148). More responders with >50% pain reduction were also observed in the pUDK-HGF groups than in the placebo groups (p = 0.0168). In the ulcer cohort of patients, pUDK-HGF treatment tended to be superior to the placebo in the percentage of patients with both complete ulcer healing and >50% ulcer healing. No significant differences in the incidence of adverse events (AEs) or serious AEs were observed among the groups. The mid-dose pUDK-HGF (6 mg) was the most efficacious, and is therefore an appropriate dose for use in a phase III clinical trial. This study was approved by the China Food and Drug Administration (2013L00637), China Clinical Trial Registry URL: www.chinadrugtrials.org.cn. Unique Identifier: 20130378.

[Preliminary evaluation of clinical effects of below-knee arterial bypass on diabetic lower limb ischemia].

OBJECTIVE: To evaluate medium-long term patency of below-knee bypass on patients who suffered from diabetic lower limb ischemia. METHODS: Clinical and follow-up data of 51 patients was retrospectively analyzed who underwent 56 below-knee bypass because of diabetes from November 2001 to December 2006. There were 35 male and 16 female with an average age of 68 years. They endured 26 months ischemic time lag in average, and had suffered from diabetes for 11 years. All of the patients were performed bypass to below-knee (posterior tibial, anterior tibial or peroneal) arteries. Kaplan-meier method was applied. The subgroups of different operative methods and different out-flow vessels were compared by Log-rank tests. RESULTS: An average follow-up time of 23 months was achieved, and lost-follow-up rate was 15%. The total 1- and 5-year primary patent rates were 68% and 54% respectively, secondary patent rate were 70% and 60% respectively, limb salvage rates were 69% and 65%, survival rates were 82% and 60%. One year (3 years) of patent rate(s) of operative method subgroups of femoral-popliteal-infrageniculate bypass with composite grafts, femoral/popliteal-infrageniculate bypass with artificial grafts and femoral/popliteal-infrageniculate bypass with autologous veins were 70% (50%), 33% (33%) and 70% (70%) respectively. One year (4 years) of patent rate(s) of out-flow vessel subgroups of posterior tibial artery, anterior tibial artery and peroneal artery were 65% (60%), 80% (53%) and 77% (66%) respectively. However, both subgroups did not show any statistic differences by log-rank tests. CONCLUSIONS: Partial or whole autologous veins as bypass grafts should be chosen when infrageniculate bypass is considered in diabetic patients. Considerable patent rates are acceptable no matter what kinds of out-flow vessels are chosen.

Red blood cell distribution width predicts long-term mortality in critically ill patients with acute kidney injury: a retrospective database study.

Acute kidney injury (AKI) is a serious complication in the intensive care unit (ICU), which may increase the mortality of critically ill patients. The red blood cell distribution width (RDW) has proved useful as a predictor of short-term prognosis in critically ill patients with AKI. However, it remains unknown whether RDW has a prognostic value of long-term all-cause mortality in these patients. The data of 18279 critically ill patients with AKI at first-time hospital admission were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The tertiles of the RDW values were used to divide subjects into three groups, namely RDW < 13.6% for the low RDW group, 13.6% ≤ RDW < 15.2% for the middle RDW group and RDW ≥ 15.2% for the high RDW group. Demographic data, mortality, 4-year survival time and severity scale scores were compared among groups. The Kaplan-Meier analysis and the Cox regression analysis were performed to assess the impact of RDW on all-cause mortality in AKI patients. The receiver operating characteristic (ROC) curve analysis was done to evaluate the prognostic value of RDW on the long-term outcome of critically ill patients with AKI. The median age of the enrolled subjects was 65.6 years. AKI patients with a higher RDW value had significantly shorter survival time and higher death rate. By the Kaplan-Meier analysis, patients in the higher RDW group presented significantly shorter survival time and higher death rate. The Cox regression model indicated RDW as an independent risk factor of all-cause mortality of AKI patients (HR 1.219, 95% CI, 1.211 to 1.228). By the ROC analysis, RDW appeared more efficient in predicting long-term prognosis as compared with conventional severity scales. The AUC of RDW (95% CI, 0.712 to 0.725) was significantly higher than other severity scale scores. In conclusion, RDW is positively correlated to survival time of 4-year follow-up in critically ill patients with AKI, and RDW is an independent prognostic factor of long-term outcomes of these patients.