High-Performance Monolithic 3D Integrated Complementary Inverters Based on Monolayer n-MoS2 and p-WSe2.

Herein, the structure of integrated M3D inverters are successfully demonstrated where a chemical vapor deposition (CVD) synthesized monolayer WSe2 p-type nanosheet FET is vertically integrated on top of CVD synthesized monolayer MoS2 n-type film FET arrays (2.5 × 2.5 cm) by semiconductor industry techniques, such as transfer, e-beam evaporation (EBV), and plasma etching processes. A low temperature (below 250 °C) is employed to protect the WSe2 and MoS2 channel materials from thermal decomposition during the whole fabrication process. The MoS2 NMOS and WSe2 PMOS device fabricated show an on/off current ratio exceeding 106 and the integrated M3D inverters indicate an average voltage gain of ≈9 at VDD = 2 V. In addition, the integrated M3D inverter demonstrates an ultra-low power consumption of 0.112 nW at a VDD of 1 V. Statistical analysis of the fabricated inverters devices shows their high reliability, rendering them suitable for large-area applications. The successful demonstration of M3D inverters based on large-scale 2D monolayer TMDs indicate their high potential for advancing the application of 2D TMDs in future integrated circuits.

Development of a preoperative prognostic scoring system to predict benefits of hepatic resection in advanced hepatocellular carcinoma patients.

OBJECTIVE: The present study aimed to identify risk factors for overall survival in advanced hepatocellular carcinoma (HCC) patients and establish a scoring system to select patients who would benefit from hepatic resection. METHODS: Survival curves were analyzed using the Kaplan-Meier method and log-rank test. The prognostic scoring system was developed from training cohort using a Cox-regression model and validated in a external validation cohort Results: There were 401 patients in the training cohort, 163 patients in the external validation cohorts. The training cohort median survival in all patients was 12 ± 1.07 months, rate of overall survival was 49.6% at 1 year, 25.0% at 3 years, and 18.0% at 5 years. A prognostic scoring system was established based on age, body mass index, alkaline phosphatase, tumor number and tumor capsule. Patients were classified as low- risk group(≤3.5) or high-risk group(>3.5). High-risk patients had a median survival of 9 months, compared with 23 months in low-risk patients. The area under the receiver operating characteristic curve (AUC) of the prognostic scoring system was 0.747 (0.694-0.801), which is significantly better than AFP, Child-Pugh and ALBI. The AUC of validation cohorts was 0.716 (0.63-0.803). CONCLUSION: A prognostic scoring system for hepatic resection in advanced HCC patients has been developed based entirely on preoperative variables. Patients classified as low risk using this system may experience better prognosis after hepatic resection.

Evaluation of liver regeneration and post-hepatectomy liver failure after hemihepatectomy in patients with hepatocellular carcinoma.

Aim: To explore clinical factors associated with extent of liver regeneration after hemihepatectomy to treat hepatocellular carcinoma (HCC).Methods: Future liver remnant volume (as a percentage of functional liver volume, %FLRV) and remnant liver volume were measured preoperatively and at 1, 5, 9, and 13 weeks postoperatively.Results: After hepatectomy, 1 of 125 patients (0.8%) died within 3 months, 13 (10.4%) experienced liver failure, and 99 (79.2%) experienced complications. %FLRV was able to predict liver failure with an area under the receiver operating characteristic curve of 0.900, and a cut-off value of 42.7% showed sensitivity of 85.7% and specificity of 88.6%. Postoperative median growth ratio was 21.3% at 1 week, 30.9% at 5 weeks, 34.6% at 9 weeks, and 37.1% at 13 weeks. Multivariate analysis identified three predictors associated with liver regeneration: FLRV < 601 cm3, %FLRV, and liver cirrhosis. At postoperative weeks (POWs) 1 and 5, liver function indicators were significantly better among patients showing high extent of regeneration than among those showing low extent, but these differences disappeared by POW 9.Conclusions: FLRV, %FLRV, and liver cirrhosis strongly influence extent of liver regeneration after hepatectomy. %FLRV values below 42.7% are associated with greater risk of post-hepatectomy liver failure.

Adjuvant transarterial chemoembolization for patients with hepatocellular carcinoma involving microvascular invasion.

BACKGROUND: Microvascular invasion (MVI) has recently been reported to be an independent prognostic factor in patients with hepatocellular carcinoma (HCC). This study compared the outcomes of adjuvant transarterial chemoembolization (A-TACE) after hepatic resection (HR) in patients with HCC involving MVI. METHODS: This prospective study involved 200 consecutive patients with MVI-HCC who underwent HR alone (n = 109) or HR with A-TACE (n = 91).The Kaplan-Meier method was used to compare disease-free survival (DFS) and overall survival (OS). RESULTS: The two groups showed similar DFS at 1, 2, and 3 years (P = 0.077). The A-TACE group showed significantly higher OS than the HR-only group (P = 0.030). Subgroup analysis showed that A-TACE was associated with significantly higher DFS and OS among patients with a tumor diameter >5 cm or with multinodular tumors. CONCLUSIONS: A-TACE may improve postoperative outcomes for MVI-HCC patients, especially those with tumor diameter >5 cm or multinodular tumors.

Preseeding of human vascular cells in decellularized bovine pericardium scaffold for tissue-engineered heart valve: an in vitro and in vivo feasibility study.

Human vascular cells from saphenous veins have been used for cell seeding on the synthetic scaffolds for constructing tissue-engineered heart valve (TEHV). However, little is known about the seeding of human vascular cells on bovine pericardium, a potential natural scaffold for TEHV. This study was aimed to assess the basic in vitro and in vivo characteristics of the human vascular cells seeded on decellularized bovine pericardium. In vitro, bovine pericardium samples with cell seeding were inspected on day 7, 14, and 21 by histology, scanning electron microscopy, and immunohistochemistry. In vivo, experiments were performed in nude mice by bilateral dorsal incision for the implantation of decellularized bovine pericardium with and without cell seeding. Results demonstrated that a total of 8-10 × 10(6) cells were obtained within 4-5 wk by the primary co-culture, which were detected positive for von Willebrand factor, α-smooth muscle actin antibodies, and fibronectin, indicating the presence of endothelial cells, smooth muscle cells, and fibroblasts, respectively. In vitro, the seeded cells showed a steady increase of endothelial activity from day 1 to day 7 and remained stable until day 21. After 30 days of implantation in vivo, the cells on the decellularized bovine pericardium could differentiate directionally and show all the identities of human endothelial cells, smooth muscle cells, and fibroblasts. These results indicate that the human vascular cells from the saphenous vein are an optional cell source for seeding on decellularized bovine pericardium scaffold for constructing TEHV.

An in vitro model for studying neutrophil activation during cardiopulmonary bypass by using a polymerase chain reaction thermocycler.

The accurate temperature control of a polymerase chain reaction (PCR) thermocycler was exploited in developing an in vitro model to study neutrophil activation during cardiopulmonary bypass. Neutrophils from 12 volunteers underwent temperature changes in a PCR thermocycler (37 degrees C for 30 minutes, 28 degrees C for 60 minutes, and then 37 degrees C for 90 minutes). Different co-incubates were applied to neutrophils, as follows: Group A: phosphate-buffered saline solution; Group B: platelet activating factor (PAF) ; Group C: platelet-depleted plasma; Group D: platelet-depleted plasma + PAF; and Group E: platelet-rich plasma. Membrane-bound elastase (MBE) activity was measured every 30 minutes throughout the experiment. MBE activity decreased significantly after hypothermia, compared with the baseline level (p < 0.001), and it resumed an increase after re-warming. Among all co-incubates, platelet-rich plasma was the most potent pro-inflammatory stimulus to neutrophils. A linear correlation was found between MBE and platelet count in platelet-rich plasma (p = 0.004). A novel in vitro model involving a PCR thermocycler has been proved to be reliable in the study of neutrophil activation during cardiopulmonary bypass. The model could possibly be used as an alternative to animals in the development of new drugs to combat neutrophil damage to tissues and organs during cardiopulmonary bypass in cardiac surgery.

Favorable effects of the detergent and enzyme extraction method for preparing decellularized bovine pericardium scaffold for tissue engineered heart valves.

Bovine pericardium has been extensively applied as the biomaterial for artificial heart valves and may potentially be used as a scaffold for tissue-engineered heart valves after decellularization. Although various methods of decellularization are currently available, it is unknown which method is the most ideal one for the decellularization for bovine pericardium. We compared three decellularization methods, namely, the detergent and enzyme extraction (DEE), the trypsin (TS), and the Triton X-100 and sodium-deoxycholate (TSD) method, to examine their efficacy on cell removal and their preservation of the mechanical function and the tissue matrix structure. Results indicated that decellularization was achieved by all the three methods as confirmed by hematoxylin-eosin staining, scanning electron microscopy, as well as quantitative DNA measurement. However, TS and TSD methods resulted in severe structural destruction of the bovine pericardium as shown by von Gieson staining and Gomori staining. Furthermore, both TS and TSD methods changed the mechanical property of the bovine pericardium, as evidenced by a lower elastic modulus, maximal-stress, maximal-disfiguration, maximal-load, and maximal-strain. In conclusion, the DEE method achieved both a complete decellularization and preservation of the mechanical function and tissue structure of the bovine pericardium. Thus, this method is superior to either the TS or the TSD method for preparing decellularized bovine pericardium scaffold for constructing tissue-engineered heart valves.

Heparin coating of small-caliber decellularized xenografts reduces macrophage infiltration and intimal hyperplasia.

Small-caliber decellularized xenografts with surface heparin coating are known to reduce in vivo thrombogenicity. This study was performed to examine whether heparin coating on the small-caliber decellularized xenografts would reduce macrophage infiltration and intimal hyperplasia. In a rabbit model of bilateral carotid implantation, each of the animals (n = 18) received a heparin-coated decellularized xenograft from a canine carotid artery on one side and a nonheparin-coated one on the other side. These experiments were terminated respectively at 1 week (n = 6), 3 weeks (n = 6), and 12 weeks (n = 6). Results showed that, compared with the nonheparin-coated grafts, the heparin-coated grafts had significantly less macrophage infiltration 1 week after implantation, identified by the mouse antirabbit macrophage antibody (RAM11)-positive cells on the vascular wall, covering all the proximal, middle, and distal parts of the grafts (P < 0.01). Moreover, the heparin-coated grafts also showed less deposition of proliferation cell nuclear antigen (PCNA)-positive cells on the vascular wall, indicating less cell proliferation, which was significant not only at 1 week (P < 0.01) but also at 12 weeks (P < 0.01). Intimal hyperplasia, measured by the intimal : media (I : M) ratio, was found similar in both groups at 1 and 3 weeks. However, the I : M ratio was significantly lower in the heparin-coated group than in the nonheparin-coated group at 12 weeks, especially in the proximal anastomosis area (0.76 +/- 0.12 vs. 0.345 +/- 0.06, P < 0.01). Heparin coating of small-caliber decellularized xenografts is associated with an early reduction of macrophage infiltration and intimal hyperplasia in a rabbit model of bilateral carotid artery implantation for 12 weeks. Thus, heparin coating appears to deliver not only the antithrombogeneity but also the antiproliferative property for small-caliber decellularized xenografts.

Implantation of decellularized small-caliber vascular xenografts with and without surface heparin treatment.

Heparin treatment of decellularized xenografts has been reported to reduce graft thrombogenicity. However, little is known about the in vivo comparison of heparin-treated with non-heparin-treated xenografts, especially for small-caliber vascular implants. We implanted either a heparin-treated or a non-heparin-treated canine carotid artery as bilateral carotid xenograft in rabbits (n = 24). Small-caliber xenografts (3 approximately 4 mm) were decellularized by enzymatic and detergent extraction and were further covalently linked with heparin. During implantation, thrombosis rate was 4% in the heparin-treated xenografts and 25% in the non-heparin-treated xenografts after 3 weeks (P < 0.05). After 6 months, it was 8 versus 58%, respectively (P < 0.01). Both heparin-treated and non-heparin-treated xenografts harvested at the end of 3 and 6 months showed a satisfactory cellular reconstruction of either smooth muscle cells or endothelial cells. These results indicate that heparin treatment of the small-caliber decellularized xenograft reduces the in vivo thrombogenicity. Both heparin-treated and non-heparin-treated xenografts seem to undergo a similar cellular remodeling process up to 6 months.

Study on mechanical circulatory support and currently available supporting parts in China.

The research and development on extracorporeal and assisted circulation in China have been painstaking. On one hand, China has the largest population of 1.3 [corrected] billion in the world, and the demands for supporting equipment are huge. On the other hand, as a developing country, China is not wealthy. It is urgent to design and fabricate affordable circulatory support parts, machines, and artificial hearts for Chinese market. In this regard, we have made our own heart-lung machine, mechanical and tissue valves, oxygenators, and artificial hearts and their improved versions. The cost of these parts is much lower as compared with those in the Western market. Although the results of clinical application are good so far, the quality of these lifesaving parts needs to be continuously improved.