Reduced risk of overt hepatic encephalopathy and death after transjugular intrahepatic portosystemic shunt in patients with hepatic venovenous communications.

PURPOSE: Hepatic venovenous communications (HVVC) is detectable in more than one-third of cirrhotic patients, where portal hypertension (PHT) tends to present more severely. We aimed to explore the prognostic implications of HVVC in patients with sinusoidal PHT treated by transjugular intrahepatic portosystemic shunt (TIPS). METHOD: The multicenter data of patients (2020-2022) undergoing balloon-occluded hepatic venography during TIPS were retrospectively analyzed. Pre-TIPS total bile acids (TBA) levels in portal, hepatic and peripheral veins were compared between groups. The primary endpoint was the development of overt hepatic encephalopathy (HE) within one year after TIPS. RESULTS: 183 patients were eligible and classified by the presence (n = 69, 37.7 %) or absence (n = 114, 62.3 %) of HVVC. The agreement between wedged hepatic venous pressure and portal venous pressure was poor in HVVC group (intraclass correlation coefficients [ICC]: 0.141, difference: 13.4 mmHg, p < 0.001), but almost perfect in non-HVVC group (ICC: 0.877, difference: 0.4 mmHg, p = 0.152). At baseline, patients with HVVC had lower Model for end-stage liver disease scores (p < 0.001), blood ammonia levels (p < 0.001), TBA concentrations in the hepatic (p = 0.011) and peripheral veins (p = 0.049) rather than in the portal veins (p = 0.516), and a higher portosystemic pressure gradient (p = 0.035), suggesting more effective intrahepatic perfusion in this group. Within 1-year post-TIPS, HVVC group had a lower incidence of overt HE (11.7 % vs. 30.5 %, p = 0.004, HR: 0.34, 95 % CI: 0.16-0.74, absolute risk difference [ARD]: -17.4) and an improved liver transplantation-free survival rate (97.1 % vs. 86.8 %, p = 0.021, HR: 0.16, 95 % CI: 0.05-0.91, ARD: -10.3). CONCLUSIONS: For patients with sinusoidal PHT treated by TIPS, the presence of HVVC was associated with a reduced risk of overt HE and a potential survival benefit.

Effect of electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen for diabetic foot ulcers.

Diabetic foot ulcers were a significant complication of diabetes and were accompanied by delayed wound healing. To compare the effect of topical application electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen (PLCL/Fg) dressing with alginate dressing when treating diabetic foot ulcers (DFUs). A single-center, prospective, randomized, patient-blinded clinical trial was conducted from July 1, 2023, to December 26, 2023. The clinical trial registration was completed on August 28, 2023 (ClinicalTrials.gov Identifier: NCT06014437). The eligible patients with DFUs of 1-20 cm2 present for at least 1 month and with Wagner grade 1 or 2. They were randomized 1:1 to receive PLCL/Fg or alginate dressing. Participants received PLCL/Fg dressing 1-3 times per week or alginate dressing 3 times per week for 12 weeks. A total of 52 patients (33 men [63.5 %]; mean [SD] age, 63.1 [11.9] years; mean [SD] diabetes time, 8.3 [4.6] years) with DFUs were assessed for this study. The DFUs classified as Wagner grade 1 or 2 (mean [SD] ulcer area, 3.8 [3.2] cm2) were randomized to receive either the PLCL/Fg dressing (n = 26) or the alginate dressing (n = 26) for as long as 12 weeks. In this study, the incidence of complete healing included 22 patients (91.7 %) in the PLCL/Fg group and 14 (63.6 %) in the alginate group during the 12-week treatment period (P = 0.003). The treatment-related adverse events that occurred were 5 (20.8 %) in the PLCL/Fg group and 4 (18.1 %) in the comparator group. In this randomized clinical trial, PLCL/Fg dressing showed beneficial effects in DFUs treatment of wound surface reduction and regulating the wound microenvironment.

Outcomes of Excimer Laser Ablation Combined with Drug-coated Balloon in Atherosclerotic Lesions of the Popliteal Artery.

BACKGROUND: The treatment of atherosclerotic lesions in the popliteal artery is challenging. This study aims to investigate the efficacy and safety of excimer laser ablation (ELA) combined with drug-coated balloon (DCB) for these lesions. METHODS: From June 2019 to December 2021, data of patients who underwent ELA combined with DCB in the popliteal artery were retrospectively reviewed. Demographics, lesion characteristics, periprocedural complications, and follow-up information were analyzed. The primary endpoint was primary patency. Secondary endpoints included major amputation-free survival rate, technical success, bailout stenting, clinically-driven target lesion reintervention, improvement of ankle-brachial index (ABI), and Rutherford class. RESULTS: A total of 61 patients were enrolled. The mean age was 73.4 ± 11.7 years. 20 (32.8%) patients had stenotic lesions, while 41 (67.2%) patients had chronic total occlusions. The mean length of these lesions was 7.3 ± 2.8 cm. Procedure technical success rate was 95.1%. Bailout stent was performed in 3 (4.9%) patients. Intraprocedural distal embolization occurred in 3 (4.9%) patients, while flow limiting dissections occurred in 3 (4.9%) patients. The mean ABI was significantly improved from 0.45 ± 0.13 at baseline to 0.90 ± 0.12 after ELA, 0.88 ± 0.11 at 6 months and 0.85 ± 0.12 at 12 months during the follow-up period. The median follow-up time was 28.2 ± 6.1 months. Reintervention was performed in 5 (8.2%) patients. The 2-year primary patency was 83.5%. CONCLUSIONS: ELA combined with DCB is a safe and effective strategy in the treatment of popliteal artery atherosclerotic lesions with low rates of bail-out stenting and high primary patency.

Platelet factor 4 promotes deep venous thrombosis by regulating the formation of neutrophil extracellular traps.

The presence of neutrophil extracellular traps (NETs) in thrombotic diseases has been extensively studied. The exact mechanism of NET formation in deep venous thrombosis (DVT) has not been largely studied. This study is aimed to explore the role of NETs and their interaction with platelet factor 4 (PF4) in DVT. In plasma samples from 51 healthy volunteers and 52 DVT patients, NET markers and PF4 were measured using enzyme-linked immunosorbent assays (ELISA). NET generation in blood samples from healthy subjects and DVT patients was analyzed by confocal microscopy and flow cytometry. The plasma levels of NETs were significantly elevated in DVT patients, and neutrophils from patients showed a stronger ability to generate NETs after treatment. PF4 was upregulated in plasma samples from DVT patients and mediated NET formation. NETs enhanced procoagulant (PCA) via tissue factor and activating platelets to induce procoagulant activity. In addition, we established an inferior vena cava ligation (IVC) model to examine the role of NETs in thrombogenicity in DVT. In conclusion, NET formation was mediated by PF4 and enhance the procoagulant activity in DVT.

Prognostic Implications of Initial Focal Contrast Enhancement in Acute Type B Intramural Hematoma.

BACKGROUND: The prognostic implication of initial focal contrast enhancement (FCE), including focal intimal disruption (FID) and intramural blood pool (IBP), in acute type B intramural hematoma (IMH) remain unclear. OBJECTIVES: The purpose of this study was to compare the prognostic implications in IMH with or without FCE. METHODS: A total of 574 patients were enrolled. FID was defined as an intimal disruption with contrast-filled out-pouching from the aorta lumen with a communicating orifice of >3 mm, and IBP was defined as a localized contrast medium-filled pool inside the IMH. RESULTS: A total of 207 (36.1%) patients with initial FCE, including 132 (63.8%) FIDs and 75 (36.2%) IBPs, were identified. Patients with FCE accompanying IMH were more likely to have hypertension (P = 0.001), pleural effusion (P = 0.006), fewer aortic segments involved (P < 0.001), more adverse aortic events (AAEs) (P < 0.001), and fewer freedom from intervention (P = 0.002). Pleural effusion (HR: 1.79; 95% CI: 1.25-2.55; P = 0.001) and FCE (HR: 1.51; 95% CI: 1.12-2.02; P = 0.006) were identified to be the independent risk factors of AAEs. In the subgroup analysis, IMH with initial FID were more likely to progress than those with initial IBP (P < 0.001). FIDs located at the proximal descending aorta (HR: 2.95; 95% CI: 1.65-5.29; P < 0.001) were associated with AAEs. CONCLUSIONS: Patients with FCE accompanying IMH were more likely to progress, especially in those initial FID localized at the proximal descending aorta. (Nature course and predictors of progression of intramural hematoma: A retrospective, multicenter study; ChiCTR2300073829).

Endovascular management of sinistral portal hypertension-related variceal hemorrhage: a multicenter retrospective study.

PURPOSE: This study aimed to assess the safety and efficacy of endovascular managements, including splenic vein recanalization (SVR), partial splenic embolization (PSE), and percutaneous transsplenic gastric varices embolization combined with PSE (PSE+GVE), for management of SPH-related variceal hemorrhage (VH). METHODS: A total of 61 patients with SPH-related VH from three hospitals were enrolled and classified into three groups: the SVR group (Group 1, n=24), the PSE+GVE group (Group 2, n=17), and the PSE group (Group 3, n=20). Baseline characteristics and clinical outcomes were compared among the groups. RESULTS: The technical success rates for transhepatic and transsplenic SVR were 27.8% and 34.6%, respectively. No major complications were observed during any of the procedures. The median follow-up period was 53.2 months. The 2-year GI rebleeding rates for Group 1, 2, and 3 were 0%, 5.9%, and 35%, respectively. Groups 1 and 2 have a lower GI rebleeding rate (p = 0.002, p = 0.048, respectively) and better results of the degree of GV (p = 0.003, p = 0.044, respectively) compared to Group 3. No significant differences were found in 2-year GI rebleeding rates and the degree of GV between Group 1 and 2 (p = 0.415, p = 0.352, respectively). CONCLUSION: SVR, PSE+GVE, and PSE seem safe and effective for management of SPH-related VH. SVR appears to be the superior treatment option. Transsplenic access may further increase the SVR success rate. PSE+GVE seems to have comparable outcomes in GV control and GI rebleeding rates compared to SVR, while superior to PSE.

The prevalence rate, mortality, and 5-year overall survival of Schistosoma japonicum patients with human malignancy.

Background: Only a few studies have focused on the association between Schistosoma japonicum and human malignancy. The aim of this study was to update the prevalence rate, mortality, and 5-year overall survival of S. japonicum patients with human malignancy. Methods: From January 20, 2018, to January 31, 2021, 5,866 inpatients were included in the study. A total of 656 S. japonicum patients with malignancy were identified. Cases were stratified by gender and age groups. The cancer sites, prevalence rate, mortality, and 5-year overall survival of the patients were reported. The S. japonicum patients with malignancy were further divided into a non-digestive system tumor group (n = 309) and a digestive system tumor group (n = 347), including those with cancer in the esophagus, stomach, colon, rectum, liver, gallbladder, bile duct, or pancreas. Chi-squared test and odds ratio with confidence intervals were performed between these two groups. Results: Lung cancer was found the most common malignancy, accounting for 18.6% of all malignancies, followed by colorectal, stomach, liver, and gallbladder cancers. These five leading malignancies accounted for approximately 61.8% of all cases. Colorectal cancer was the leading cause of malignancy death, followed by lung, stomach, gallbladder, and liver cancers. These five leading causes of death accounted for approximately 55.6% of all death cases. Statistical significance was found in the prevalence rate between S. japonicum and non-S. japonicum patients with/without digestive system tumor (p < 0.001). The odds ratio of S. japonicum patients with digestive system tumors was 1.6 (95%CI: 1.4-1.9). Conclusion: S. japonicum contributes to a significant prevalence and mortality in digestive system tumors, including colorectal, stomach, liver, and gallbladder cancers.

Risk factors for at-risk foot and peripheral artery disease among the population with diabetes: A multicommunity-based cross-sectional study.

AIMS: This study aimed to investigate the prevalence, characteristics, and influence factors of the at-risk foot with diabetes mellitus (DM). METHODS: This study included 3030 DM patients from the at-risk foot screening program of Shanghai in China between March 21 and April 30 in 2021. Data were collected from the questionnaire survey, physical examination, and fasting blood sample. RESULTS: The prevalence of at-risk foot was 27.8% among DM patients. After adjusted, the risk of higher at-risk grade increased with age and urinary albumin creatinine ratio (OR = 1.04, 95%CI = 1.02-1.06; OR = 1.001, 95%CI = 1.000-1.002, respectively), whereas decreased with estimated glomerular filtration rate (eGFR) (OR = 0.991, 95%CI = 0.984-0.998). The incidence of peripheral artery disease (PAD) was 11.1% in all people with DM, and age, pulse rate, and low-density lipoprotein were independent risk factors for PAD. In contrast, high-density lipoprotein, eGFR, and lymphocyte-to-monocyte ratio were independent protective factors for PAD. Glycated hemoglobin HbA1c was not an independent risk factor for increased risk grade or more severe PAD. CONCLUSIONS: The at-risk foot accounted for a high percentage among DM patients. Advanced age and renal dysfunction are independent risk factors for the at-risk foot. Glycemic control does not reduce the risk grade of at-risk foot and the incidence of PAD.

Preclinical animal study of electrospun poly (l-lactide-co-caprolactone) and formulated porcine fibrinogen for full-thickness diabetic wound regeneration.

Diabetic foot ulcer is one of the most serious chronic complications of diabetes mellitus. It may lead to amputation of the lower extremities for diabetics. Our study was to evaluate the effect of electrospun poly (L-lactide-co-caprolactone) and formulated porcine fibrinogen (PLCL/Fg) wound dressing on animal wound model. A blend ratio of PLCL/Fg scaffold was 4 (PLCL):1 (Fg). The scanning electron microscopy findings showed that the fibers' diameter was 122.5 ± 80.3 nm, and the tensile strength was 9.2 ± 0.2 MPa. In-vivo study of the hog normal model demonstrated that PLCL/Fg dressing had better biocompatibility, degradability, and ability to restore the skin's normal structure. We evaluated the wound healing processes in the rat diabetic model by macroscopic observation and histological observation at 1, 2, and 3 post-operation weeks. In our study, the PLCL/Fg group performed better 3 weeks after surgery, in terms of macroscopic healing and scarring. After surgery, the PLCL/Fg group showed better fibroblast accumulation, tissue granulation, and collagen expression than the control group. Topical treatment with PLCL/Fg dressing effectively enhanced wound healing in both normal and hyperglycemic conditions, suggesting that it may possess wound-healing potential.

Characterization of prognostic value and immunological roles of RAB22A in hepatocellular carcinoma.

Background: The protein-coding gene RAB22A, a member of the RAS oncogene family, is amplified or overexpressed in certain cancers. However, its action mechanism in hepatocellular carcinoma (HCC) remains unclear. Here, we aimed to examine the connection between RAB22A and survival prognosis in HCC and explore the biological significance of RAB22A. Methods: A database-based pan-cancer expression analysis of RAB22A was performed. Kaplan-Meier analysis and Cox regression were performed to evaluate the association between RAB22A expression and survival prognosis in HCC. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), various potential biological functions and regulatory pathways of RAB22A in HCC were discovered. Tumor immune infiltration was studied using the single sample gene set enrichment analysis (ssGSEA) method. N6-methyladenosine modifications and the regulatory network of competitive endogenous RNA (ceRNA) were verified in the TCGA cohort. Results: RAB22A was upregulated in HCC samples and cell lines. A high RAB22A expression in HCC was strongly correlated with sex, race, age, weight, TNM stage, pathological stage, tumor status, histologic grade, TP53 mutation status, and alpha fetal protein (AFP) levels. Overexpression of RAB22A indicated a poor prognosis was related to overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). GO and KEGG analyses revealed that the differentially expressed genes related to RAB22A might be involved in the proteasomal protein catabolic process, ncRNA processing, ribosome ribosomal subunit, protein serine/threonine kinase activity, protein serine kinase activity, Endocytosis, and non-alcoholic fatty liver disease. GSEA analyses revealed that the differentially expressed genes related to RAB22A might be involved in the T cell receptor, a co-translational protein, that binds to the membrane, axon guidance, ribosome, phagocytosis, and Eukaryotic translation initiation. RAB22A was correlated with N6-methyladenosine expression in HCC and established RAB22A-related ceRNA regulatory networks. Finally,RAB22A expression was positively connected the levels of infiltrating with T helper cells, Tcm cells, and Th2 cells,In contrast, we observed negatively correlations with cytotoxic cells, DCs, and pDCs cells.Moreover,RAB22A expression showed a strong correlation with various immunomarkergroups in HCC. Conclusions: RAB22A is a potential therapeutic target for improving HCC prognosis and is closely related to immune cell infiltration.

Network Analysis and Nomogram in the Novel Classification and Prognosis Prediction of Advanced Schistosomiasis Japonica.

Clinical classification of advanced schistosomiasis japonica is important for treatment options and prognosis prediction. Network analysis was used to solve the problem of complexity and co-occurrence complications in classification of advanced schistosomiasis. A total of 4,125 retrospective patients were enrolled and divided randomly into a training cohort (n = 2,888) and a validation cohort (n = 1,237). Network analysis was used to cluster the isolated complications of advanced schistosomiasis. The accuracy of the network was evaluated. Nomograms based on the clustered complications were built to predict 1- to 5-year survival rates in advanced schistosomiasis. The predictive performance of the nomogram was also evaluated and validated. Fifteen isolated complications were identified: metabolic syndromes, minimal hepatic encephalopathy, hepatic encephalopathy, chronic obstructive pulmonary disease, pulmonary hypertension, respiratory failure, right heart failure, gastroesophageal variceal bleeding, gastrointestinal ulcer bleeding, splenomegaly, fibrosis, chronic kidney disease, ascites, colorectal polyp, and colorectal cancer. Through network analysis, three major clustered complications were achieved-namely, schistosomal abnormal metabolic syndromes (related to chronic metabolic abnormalities), schistosomal abnormal hemodynamics syndromes (related to severe portal hypertension and portosystemic shunting), and schistosomal inflammatory granulomatous syndromes (related to granulomatous inflammation). The nomograms showed a good performance in prognosis prediction of advanced schistosomiasis. The novel classification-based nomogram was useful in predicting the survival rate in advanced schistosomiasis japonica.

A new alternative technique for the guidance of transjugular intrahepatic portosystemic shunt creation using DSA overlay reference.

BACKGROUND: Portal vein puncture (PVP) is a critical step during transjugular intrahepatic portosystemic shunt (TIPS) and correlates to several complications. Techniques guiding PVP are needed. PURPOSE: To evaluate the safety, feasibility, and efficiency of digital subtraction angiography (DSA) overlay reference during TIPS creation and compare it with transhepatic portal vein (THPV) guiding. MATERIAL AND METHODS: The clinical records of 185 patients at three medical centers who underwent TIPS placement were reviewed. Portal vein access was guided by THPV guiding in 120 cases and DSA overlay reference in 60 cases. The number of punctures, portal vein entry time, procedural adverse events, technical and hemodynamic success rate were analyzed to compare the safety, feasibility, and efficiency of the two methods. RESULTS: The median numbers of punctures in group 1 and group 2 were 2 (1-4) and 2 (1-5), respectively (P = 0.094). There was no statistical difference between two groups in needle passes. The median portal vein entry time of group 1 was 12 min (8-16 min) and 13 min (8-16 min) in group 2. No significant difference was found in the PVP time (P = 0.802). Arterioportal fistula formation occurred in 15 patients in group 1; two patients in group 2 had hepatic artery injury. The patients in group 2 had lower rates of procedural adverse events (P = 0.047). Median dose area product of G1 was lower than G2 statistically (P<0.001). There was no significant difference in total fluoroscopy time (P = 0.856). CONCLUSION: DSA overlay reference has lower procedural adverse events rates compared with THPV guiding TIPS. It seems to be a safe and effective method for guiding PVP.

Safety and Effectiveness of Excimer Laser Ablation Combined With Drug-Coated Balloon for Atherosclerotic Obliterans in the Lower Extremity.

PURPOSE: To evaluate the safety and effectiveness of excimer laser ablation (ELA) combined with drug-coated balloon (DCB) for atherosclerotic obliterans (ASO) of the lower extremities. MATERIALS AND METHODS: From June 2019 to December 2020, all eligible patients were enrolled. Demographics, characteristics of lesions, complications, and follow-up information were collected and analyzed. The primary endpoint was major amputation-free survival (MAFS). Secondary endpoints included technical success, primary patency, bailout stent, distal embolization, target lesion reintervention (TLR), and ulcer healing rate. Major amputation-free survival and primary patency were calculated by Kaplan-Meier analysis. RESULTS: A total of 71 patients were enrolled. Forty-eight (81.7%) patients presented critical limb ischemia (CLI) and 48.6% of them was calcification class 4 according to Peripheral Arterial Calcium Scoring System (PACSS). Chronic totally occluded (CTO) disease was the most common lesion in 66.0% of them and superficial femoral artery (SFA) was the most common segment in 59.6%. Technical success rate was 93.0%. One-year follow-up was finished in 25 (35.2%) patients. The primary patency and MAFS were 92.0%±27.6% and 96.0%±20.0% at 12 months, respectively. During the mean follow-up of 9.4±4.3 months, clinically-driven TLR occurred in 2 (2.8%) patients, and major and minor amputation occurred in 2 (2.8%) and 1 (1.4%) patient, respectively. CONCLUSION: The early results demonstrated that ELA was an effective treatment in de novo, in-stent restenosis (ISR) and CTO lesions. Meanwhile, ELA could prepare the lumen for the use of DCB and reduce the implantation of stents, especially in segments unsuitable for stenting. Mid-term and long-term results need to be awaited.

Results of Excimer Laser Ablation Combined with Drug-Coated Balloon for Atherosclerotic Obliterans of Lower Extremity and Risk Factors for Loss of Primary Patency.

BACKGROUND: The results of excimer laser ablation (ELA) combining with drug-coated balloon (DCB) in the treatment for atherosclerotic obliterans (ASO) remains unclear. METHODS: Retrospectively enrolled patients who underwent ELA combined with DCB in 2 centers. The primary endpoint was primary patency, and secondary endpoints included technical success, procedure-related complications, major amputation, clinically driven target lesions reintervention (CD-TLR), measurements of ankle-brachial index (ABI), and quality of life (QoL). RESULTS: 102 patients were enrolled. The primary patency was 86.7% (95% confidence interval [CI]: 72.9%-89.0%) at 12 months and 82.6% (95% CI: 78.2%-92.1%) at 24 months. The freedom from reintervention was 87.8% (95% CI: 79.5%-92.9%) at 12 months and 86.6% (95% CI: 78.1%-92.0%) at 24 months. The ABI measurement and QoL were significantly improved at each follow-up point. Sixteen (15.7%) patients lost the primary patency. Patients losing the primary patency demonstrated higher Rutherford class (P = 0.004), worse runoff (P < 0.001), higher Peripheral Arterial Calcium Scoring System (PACSS) (P < 0.001), and smaller ratio of tube diameter to reference vessel diameter (TD/RVD) (P < 0.001) compared with patients without losing it. The run-off ≥7 (adjusted odds ratio [aOR]: 34.3; 95% CI: 2.9-398.3; P = 0.005) and TD/RVD <4.9 (aOR: 24.7; 95% CI: 1.7-359.5; P = 0.019) were independent risk factors for loss of primary patency. CONCLUSIONS: ELA combined with DCB seemed an effective and safe treatment for ASO of lower extremity, and it could not only reduce the implantation of stent but significantly improve QoL. The run-off ≥7 and TD/RVD <4.9 were independent risk factors for loss of primary patency.

Excimer laser ablation combined with drug-coated balloon versus drug-coated balloon in the treatment of de novo atherosclerotic lesions in lower extremities (ELABORATE): study protocol for a real-world clinical trial.

BACKGROUND: The efficacy and validity of excimer laser ablation (ELA) in the in-stent restenosis (ISR) has been confirmed. However, its application in de novo atherosclerotic lesions of lower extremity artery disease (LEAD) has not been clearly defined and its procedure has not been standardized. METHODS: ELABORATE is a prospective, multicenter, real-world study designed to evaluate the efficacy and safety between ELA combined with drug-coated balloon (DCB) and DCB alone in de novo atherosclerotic lesions of LEAD. DISCUSSION: ELABORATE is a prospective, multicenter, real-world study designed to assess the efficacy and safety between ELA combined with drug-coated balloon (DCB) and DCB alone in patients with de novo atherosclerotic lesions of LEAD. According to the real-world situation, eligible patients will be allocated to ELA + DCB group (group E) and DCB group (group C). Baseline and follow-up information (at 3, 6, and 12 months) will be collected. The primary efficacy point is primary patency at 12-months, and the secondary efficacy points include clinically driven target lesion reintervention (CD-TLR), change of Rutherford class, ankle-brachial index and ulcer healing rate. These indexes will be assessed and recorded at 3, 6, and 12-month follow-up. Also, safety evaluation, including major adverse event, all-cause mortality through 30-day follow-up, unplanned major amputation, bailout stent and distal embolization, will also be evaluated by an independent core laboratory. All the data will be collected and recorded by the electric data capture system. This study will be finished in 3 years and the 12-month results will be available in 2023. All the patients will be followed for 5 years. Trial registration number Chinese Clinical Trial Registry (ChiCTR2100051263). Registered 17 September 2019. http://www.chictr.org.cn/listbycreater.aspx .

Improved Extraction of Second-Order Material Constants for Current Generation Y-Grown La3Ga5.5Nb0.5O14 (LGN) Crystal.

With higher demand for sensor development, piezoelectric materials with advanced performance and wide availability draw more attention today. Accurate second-order material constants are necessary for modeling and mechanical design of sensors that make use of langanite (La3Ga5.5Nb0.5O14, LGN) crystals. We report here on room temperature LGN bulk acoustic wave (BAW) velocities obtained with reduced uncertainties using ultrasound measurements and taking advantage of the cross correlation signal processing technique, and a full set of LGN material constants extracted from the BAW velocity results. Our results compare favorably with prior results assessed as using a reliable measurement technique, and differ in expected fashion from other results based on techniques that do not address a known weakness in the measurement technique.

Effects of Semiconduction on Thickness-Extensional Modes of Piezoelectric Resonators.

We study thickness-extensional vibrations of a piezoelectric semiconductor plate for resonator application. A perturbation integral for the semiconduction-induced frequency shift is obtained, which shows that the first-order frequency shift represents a damping effect due to semiconduction. Numerical results for ZnO and AlN plates are presented.

Characterization of the microenvironment of diabetic foot ulcers and potential drug identification based on scRNA-seq.

Background: Diabetes foot ulcers (DFUs) are a type of foot infection, ulcer, and/or deep tissue destruction caused by neuropathy and vascular disease in the distal extremities of diabetic patients. Its pathogenesis and its microenvironment are not entirely understood. Methods: Initially, the GSE165816 data set from the GEO database was utilized for single cell analysis to reveal the microenvironment and functional status of DFUs. The GSE199939 RNA-seq data set was utilized for external validation. On the basis of the logistic regression machine learning algorithm (OCLR), pseudo time series analysis, dryness index analysis, and drug target gene analysis were then performed. By constructing drug-gene and gene-gene networks, we can locate the most recent DFUs treatments. Finally, immunofluorescence technology was used to detect the cell-related markers of the DFUs microenvironment, and qPCR was used to detect the expression of drug targets in DFUs. Results: Firstly, we used the Cell Maker database to obtain information about human cells and related gene markers, and manually reviewed a total of 45 kinds of cells and maker information that may appear in the DFUs microenvironment, which were divided into 17 cell clusters after annotation. Subsequently, we counted the proportions of DM and DFUs in different types of cells, and the results showed that the proportions of macrophages, white blood cells, and monocytes were higher in patients with DFUs, while the proportions of pluripotent stem cells and stromal cells were higher in patients with DM. The Pseudo-time series analysis of cells in DFUs showed that the differentiation pathways of immune cells, mesenchymal cells and stem cells were similar in the three states, while the other cells were distributed in different stages. At the level of a single cell, the scores of both multipotential stem cells and hematopoietic stem cells were significantly lower in DFU healing and non-healing than in DM. Additionally, the highly expressed genes in DFU were chosen as drug targets. We identified seven potential target genes and discovered twenty drugs with high significance. Finally, the colocalization relationship between CD19, ITGAM, and HLA-DR expression in monocytes and macrophages of DFU skin tissue and healthy subjects was analyzed by laser confocal microscopy with the immunofluorescence triple labeling method. The results showed that the expressions of CD19, ITGAM, and HLA-DR in the skin of DFUs were significantly higher than those in the skin of healthy subjects, and the co-localization relationship was significant in DFUs. Conclusion: This study can serve as a resource for the treatment of DFUs.

Role of M1 macrophages in diabetic foot ulcers and related immune regulatory mechanisms.

Objectives: Diabetes foot ulcers (DFUs) are characterized by immune infiltration of M1 macrophages observed in foot skin, in which immune-associated genes (IRGs) play a prominent role. The precise expression of IRGs as well as any possible regulatory mechanisms that could be present in DFUs is yet unknown. Methods: The sequencing data of single-cell RNA (scRNA) in the foot skin of patients with DFUs were analyzed, screening out the cluster marker genes of foot skin obtained from the ImmPort database. IRG activity was assessed with the AUCell software package. The IRGs of DFUs were explored by analyzing the batch sequencing dataset of DFU skin tissue. HumanTFDB was adopted to identify relevant regulatory transcription factors (TFs). The STRING dataset was used to build the main TF protein-protein interaction networks. WB and immunofluorescence methods were used to verify M1 macrophage-related immune regulators. Results: There were 16 clusters found: SMC1, fibro, t-lympho, he fibro, vasendo, baselkera, diffkera, SMC2, M1 macro, M2 macro, sweet/seba, B-Lympho, Melanio, lymphendo, plasma, and Schwann. M1 and M2 macrophages both had considerably higher AUC ratings than patients with DFUs compared to other sub-populations of cells. The proportion of M1 macrophages was the highest in the non-healing group. According to scRNA analysis and batch sequencing data by GO and KEGG, DEGs were enriched in immune response. Some 106 M1 macro-IRGs were finally identified and 25 transcription factors were revealed as associated with IRG expression. The PPI network indicated NFE2L2, REL, ETV6, MAF, and NF1B as central transcription factors. Conclusion: Based on the bio-informatics analysis of scRNA and high-throughput sequencing data, we concluded that M1 macrophages may serve as the influencing factor of DFUs' non-union. In addition, NFE2L2 could be involved in the regulation of IRG expression within M1 macrophages.