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Background: Terlipressin can effectively control acute gastrointestinal bleeding (GIB) in cirrhotic patients by acting on the V1 receptors, but may lead to the development of dilutional hyponatremi...

Introduction Acute gastrointestinal bleeding (GIB) is a major cause of death in liver cirrhosis. This multicenter study aims to develop and validate a novel and easy-to-access model for predicting the prognosis of patients with cirrhosis and acute GIB. Methods Patients with cirrhosis and acute GIB were enrolled and randomly divided into the training (n = 865) and validation (n = 817) cohorts. In the training cohort, the independent predictors for in-hospital death were identified by logistic regression analyses, and then a new prognostic model (i.e., CAGIB score) was established. Area under curve (AUC) of CAGIB score was calculated by receiver operating characteristic curve analysis and compared with Child–Pugh, model for end-stage liver disease (MELD), MELD-Na, and neutrophil–lymphocyte ratio (NLR) scores. Results In the training cohort, hepatocellular carcinoma (HCC), diabetes, total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), and serum creatinine (Scr) were independent predictors of in-hospital death. CAGIB score = diabetes (yes = 1, no = 0) × 1.040 + HCC (yes = 1, no = 0) × 0.974 + TBIL (μmol/L) × 0.005 − ALB (g/L) × 0.091 + ALT (U/L) × 0.001 + Scr (μmol/L) × 0.012 − 3.964. In the training cohort, the AUC of CAGIB score for predicting in-hospital death was 0.829 (95% CI 0.801–0.854, P

Acute gastrointestinal bleeding (GIB) rapidly reduces effective blood volume, thereby precipitating acute kidney injury (AKI). Terlipressin, which can induce splanchnic vasoconstriction and increase renal perfusion, has been recommended for acute GIB and hepatorenal syndrome in liver cirrhosis. Thus, we hypothesized that terlipressin might be beneficial for cirrhotic patients with acute GIB and renal impairment. In this Chinese multi-center study, 1644 cirrhotic patients with acute GIB were retrospectively enrolled. AKI was defined according to the International Club of Ascites (ICA) criteria. Renal dysfunction was defined as serum creatinine (sCr) > 133 μmol/L at admission and/or any time point during hospitalization. Incidence of renal impairment and in-hospital mortality were the primary end-points. The incidence of any stage ICA-AKI, ICA-AKI stages 1B, 2, and 3, and renal dysfunction in cirrhotic patients with acute GIB was 7.1%, 1.8%, and 5.0%, respectively. The in-hospital mortality was significantly increased by renal dysfunction (14.5% vs. 2.2%, P

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. During the recent years, external-beam radiation therapy (EBRT) has been safely and effectively employed for the management of HCC. We overviewed the current evidence regarding the efficacy and safety of EBRT for HCC according to the different target population. PubMed database was searched for identifying English-language full-text articles regarding EBRT for the treatment of HCC. Search items were "hepatocellular carcinoma AND radiation therapy". Until now, preliminary evidence has suggested the following role of EBRT for HCC. 1) EBRT, especially stereotactic body radiation therapy, is an emerging choice of therapy for small HCC. 2) EBRT combined with non-surgical treatment can achieve an excellent intrahepatic tumor control and a potential survival benefit for huge HCC. 3)Adjunctive EBRT may improve the efficacy of transarterial chemoembolization for HCC with portal vein tumor thrombosis. 4) EBRT can relieve the pain and improve the quality of life for patients with extrahepatic metastases. 5) EBRT may be a bridge to liver transplantation by minimizing the tumor progression. 6) Adjunctive EBRT may reduce the tumor recurrence and improve the survival after resection. In summary, EBRT is a promising choice of treatment of HCC. However, more high-quality evidence is needed to further establish the status of EBRT for the management of HCC.

Mitochondrial transcription factor A (TFAM), which is required for mitochondrial DNA (mtDNA) transcription, has been linked to metabolic changes that contribute to tumorigenesis and chemoresistance. In this work, we investigated the expression pattern and role of TFAM in hepatocellular carcinoma (HCC). TFAM expression level is similar in 18 out of 20 paired normal liver and HCC tissues with only 2 HCC tissues showing 1.8-fold increase in TFAM. Similar phenomenon was observed in HCC cell lines compared to normal liver lines. Interestingly, TFAM expression is upregulated in resistant HCC cells regardless of the differential TFAM expression level in their parental lines and mechanism of resistance. TFAM depletion led to inhibition of growth and survival but not migration, and sensitization to doxorubicin and sorafenib treatment, through AMPK activation, reduction of nucleoside triphosphates and mitochondrial respiration in HCC cells. In addition, we demonstrated that resistant HCC cell lines were more sensitive to TFAM inhibition than parental lines, and this might be due to the increased mitochondrial biogenesis in resistant HCC cell lines. Our work reveals the preferential role of TFAM in HCC cell response to standard of care drugs, which suggests a potential sensitizing therapeutic target for HCC treatment.

To compare the survival of American Joint Committee on Cancer (AJCC) stage I hepatocellular carcinoma (HCC) treated with surgery versus external beam radiation therapy (EBRT).Surveillance, Epidemiology, and End Results (SEER) database was used to identify the patients diagnosed with HCC between 2004 and 2013. Overall survival (OS) and liver-specific survival (LSS) were compared between patients treated with surgery and EBRT. A 1:1 propensity score matching (PSM) analysis was employed by matching age, sex, and race.Among the 1553 patients with HCC ≤2cm, there was no significant difference in OS (p=0.605, before PSM; p=0.891, after PSM) and LSS (p=0.281, before PSM; p=0.346, after PSM) between patients treated with surgery and EBRT. Among the 1752 patients with HCC2cm and ≤3cm, patients treated with surgery had significantly better OS (p=0.001) than those treated with EBRT, but statistically similar LSS (p=0.072) before PSM; however, there was no significant difference in OS (p=0.139) and LSS (p=0.722) between patients treated with surgery and EBRT after PSM. Additionally, 1157, 723, and 1331 patients had HCC3cm and ≤4cm, HCC4cm and ≤5cm, and HCC5cm, respectively; among them, patients treated with surgery had significantly better OS and LSS than those treated with EBRT regardless of PSM.At the AJCC stage I, the survival after EBRT might be comparable to that after surgery for HCC ≤3cm, but the survival after EBRT was inferior to that after surgery for HCC3cm.

Supplemental Digital Content is available in the text, Background and aim: Acute variceal bleeding (AVB) is life-threatening. We aimed to systematically review the current evidence regarding the efficacy and safety of terlipressin for AVB in liver cirrhosis. Methods: We searched the PubMed, EMBASE, and Cochrane Library databases. The reference list was also hand-searched. Using a random-effect model, we combined the data obtained according to the different time points when the events developed. Odds ratio (OR) and weighted mean difference (WMD) were calculated. Quality of evidence was evaluated by the GRADE methodology. Results: Thirty randomized controlled trials with 3344 patients were included. Compared with no vasoactive drug, terlipressin significantly improved the control of bleeding within 48 hours (OR = 2.94, P = .0008) and decreased the in-hospital mortality (OR = 0.31, P = .008). Compared with somatostatin, terlipressin had a significantly higher risk of complications (OR = 2.44, P = .04). Compared with octreotide, terlipressin had a significantly inferior control of bleeding within 24 hours (OR = 0.37, P = .007). Compared with vasopressin, terlipressin had a significantly lower risk of complications (OR = 0.15, P = .02). Compared with terlipressin combined with endoscopic variceal ligation, terlipressin alone had significantly higher 5-day treatment failure (OR = 14.46, P = .01) and transfusion requirements within 49 to 120 hours (WMD = 1.20, P = .002). No outcome was significantly different between terlipressin and sclerotherapy. Compared with balloon tamponade, terlipressin significantly decreased the 30-day rebleeding (OR = 0.05, P = .001) and transfusion requirements (WMD = −2.70, P = .02). Quality of evidence was very low to moderate. Conclusion: Our findings were in accordance with the current recommendations regarding terlipressin for the treatment of AVB in cirrhosis. However, due to low quality of evidence, further studies are recommended.

To explore the selection of treatment modalities for hepatocellular carcinoma (HCC) at stages T1 and/or T2 and to compare the survival of patients treated with surgery alone vs radiation therapy (RT) alone.Surveillance, Epidemiology, and End Results (SEER) database was used to identify the patients diagnosed with HCC between 2004 and 2013. The tumor-nodemetastasis (TNM) stage was established according to the American Joint Committee on Cancer (AJCC) Staging. After age, sex, TNM stage, and tumor extension were matched, the survival was further compared between patients undergoing surgery alone vs RT alone.Of 11967 patients at stages T1 (n=7829) and T2 (n=4138), 10449 (87.31%) underwent surgery alone, 1241 (10.37%) RT alone, and 277 (2.32%) surgery combined with RT. Compared with those treated with RT alone and in combination with surgery, patients treated with surgery alone were younger, with smaller tumor size, higher proportion of females, single lesion, and AJCC stage I/II, and lower proportion of regional and distant lymph nodes, bone, brain, and lung invasion. Among them, 758 pairs (surgery alone and RT alone) at stage T1 and 430 pairs (surgery alone and RT alone) at stage T2 were matched. Regardless of stage T1 or T2, patients undergoing surgery alone had a significantly better cumulative survival than those undergoing RT alone (p0.001).The treatment selection of HCC was dependent on the age, sex, tumor size, number of lesions, and extrahepatic invasion. Surgery alone should be the preferred treatment modality of HCC at stages T1 and T2.

Microcantilevers are very effective tools in detecting of small amount of bio-species and chemicals. Recent advances in metal-oxide-semiconductor field effect transistor (MOSFET) as a transducer to detect the molecule binding-induced cantilever deflection has gained extensive attention due to its high sensitivity and direct compatibility with micro-electro-mechanical system (MEMS) sensors. In this paper, six different piezoresistive nMOSFET-embedded microcantilevers are designed and characterized to systematically study the impacts of different cantilever and transistor channel geometries on the device sensitivity. It is found that the amount of change in the drain current is the same range as reported in the literature. For point-loading applications, transistors with lower channel width are optimal for relative drain current change even though their absolute current output is less. In particular, the embedded nMOSFET Exhibits 63.6% higher sensitivity by decreasing transistor channel width from 300 to 60 μm. Furthermore, theoretical results are compared with experimental data to optimize cantilever and transistor geometrical factors to achieve higher stress or force sensitivity. The low frequency noise characteristics of the devices show better resolution for higher aspect-ratio transistors, with drain current noise in the nanoampere range. Results reveal useful design guidelines to enhance the MOSFET-embedded microcantilever sensitivity for various applications.

Cantilever structures were reported to be used for flow sensing purposes. Herein, we present silicon nanowire (SiNW) based cantilever flow sensor. Five cantilever flow sensors with different depths are modeled and simulated (fluid-structure) with water flow velocity from 50 cm/s to 200 cm/s. SiNW is embedded in the cantilever as piezoresistive transducer at the anchor, and a maximum resistance change of 11.2% is obtained. Based on the results, increasing depth will not only contributes to lager cantilever deformation at fixed flow velocity, but also improves its sensitivity. However when the depth become larger to certain degree, this effect tends to saturate.

Background: Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver diseases. It has been reported that traditional Chinese medicine (TCM) may improve liver function, delay disease progression, alleviate symptoms, and improve quality of life in HRS patients. The study aims to systematically review the efficacy of TCM for the treatment of HRS. Methods: Publications were searched electronically from China National Knowledge Infrastructure (CNKI), Wanfang, VIP, PubMed, and EMBASE databases. Odds ratio (OR) and standardized mean difference (SMD) with 95% confidence interval (CI) were calculated. Heterogeneity was assessed. The Cochrane Collaboration’s tool was used to assess the risk of bias. Results: Fourteen randomized controlled trials involving 788 patients with HRS were included. Random generation sequence was reported in only two studies. Blinding was not used in any study. Compared to conventional treatment without TCM, TCM led to a significant survival benefit during hospitalization (OR: 0.18; 95% CI: 0.08–0.39; P

The prognostic impact of portal vein thrombosis (PVT) in liver cirrhosis remains controversial among studies, primarily because the risk stratification of PVT is often lacking. A definition of clinically significant PVT should be proposed and actively improved. Moreover, the risk factors for the development of PVT in liver cirrhosis should be fully recognized to screen and identify high-risk patients. Currently, well-recognized risk factors include a reduced portal vein flow velocity, a worse liver function, splenectomy, liver transplantation, and factor V Leiden and prothrombin G20210A mutations. Novel risk factors include an increased flow volume of portosystemic collateral vessel, thrombopoietin receptor agnonists, and non-selective beta-blockers. In contrast to the traditional perspectives, the abnormalities of procoagulant and anticoagulant factors may not contribute to the development of PVT in liver cirrhosis. Further studies should explore the role of other risk factors, such as antiphospholipid antibodies, methylenetetrahydrofolate reductase C677T gene mutation, hyperhomocysteinemia, and myeloproliferative neoplasms.

The piezoresistance and noise of n-type gate-all-around nanowire field-effect-transistor (NWFET) is investigated as a function of gate bias. With narrow gate bias span of 0.6 V near threshold region, the piezoresistive coefficient of NWFET enhances up to seven times from 29 × 10−11 Pa−1 to 207 × 10−11 Pa−1 under compressive and tensile strain conditions. Results reveal that the low frequency noise is reduced when operated in subthreshold region. The higher piezoresistive coefficient and reduced noise improve the sensor resolution (minimum detectable strain) by sixteen times. NWFET operates at low bias with higher piezoresistance and signal-to-noise ratio and offers promising applications in strain sensors. Published version

This paper presented the design, fabrication, and characterization of force transmitting element for MEMS tri-axial force sensor application. The transmitting element consists of two main parts: integrated silicon rod and mechanical stopper. The advantages of the design are the simplicity of fabrication process, the ability to detect force in all direction and to protect the sensing element from excessive force, thus increase the robustness of the devices.

This paper describes the design of a tri-axial microelectromechanical force sensor (FS) that can be mounted on the tip of the guidewire. Piezoresistive silicon nanowires (SiNW) are embedded into a cross cantilever design with a manoeuvrable stylus to allow the detection of force in all directions. The electrical resistance changes in the four SiNWs are used to decode an arbitrary force applied onto the FS. The sensitivity of the device can be improved by two orders of magnitude compared to bulk Si thanks to the giant piezoresistive effects offered by the SiNW. Robustness of the FS is improved due to the novel design by incorporating a mechanical stopper at the tip of the stylus. Finite element analysis (FEM) analysis was used in designing the FS.

Characterization of Lame-mode square resonators with different straight-beam anchor lengths, structural layer thickness, and number of anchor support reveals that there is likely an optimal range of anchor designs that provide high quality factor (Q) above one million, along with low motional resistance. Shorter anchor length restricts resonator vibrations and motional resistance could be increased by 3.5 times compared to resonators with longer anchor length. Two-anchor support design is able to achieve higher Qpsilas but results in higher motional resistance compared to four-anchor support. When structural thickness is reduced from 25 mum to 10 mum, Q gets degraded but still maintained above one million.

In this paper, we report for the first time the detailed analysis of the nonlinear behavior of a Lame-mode SOI bulk resonator. The measured resonant frequency of the resonator was 6.35 MHz with a quality factor of 1.7 million in the ambient pressure of 0.02 Pa. We used the two-step semi-analytic approach to characterize the model parameters of the resonator and the nonlinear model of the resonator was verified by the experimental results. Our study shows that the Lame-mode bulk resonator has three orders of magnitude larger maximum energy storage capability than the flexural beam resonator, leading to improved overall phase noise performance of the resonator-based oscillator.

Nonlinear behavior of a capacitively driven and sensed micromechanical free-free beam resonator is characterized, modeled and experimentally verified in this paper. Both the mechanical and electrostatic nonlinear effects are included in the resonator model. Instead of using the FEM tools which introduces uncertainties to the simulation process, an alternative semi-analytic method is proposed to identify the resonator parameters from just a few preliminary testing results. A 615kHz free-free beam resonator was designed, fabricated and studied. From the experimental results, it is observed that the nonlinear effects in the free-free beam always shift the resonant peak of the beam to a higher frequency under nonlinear vibration. In order to validate the proposed modeling approach, a nonlinear model was constructed based on the experimentally extracted parameters and numerically solved in MATLAB. The simulation results were compared with the experimental data, showing that the measured large-signal frequency domain response can be accurately reproduced by simulation. Although this work focused on the free-free beam resonator, the proposed modeling approach is not specific to flexural designs, but is valid for all types of electrostatic resonators. Such a method to predict nonlinear effects of microresonators will be especially useful for MEMS oscillator and filter applications.

Objective: A retrospective study was performed to compare the difference in platelet count (PLT), prothrombin time (PT), in- ternational normalized ratio (INR), and activated partial thromboplastin time (APTT), between cirrhotic patients with and without acute upper gastrointestinal bleeding (AUGIB) or acute oesophageal variceal bleeding (AEVB). Methods: Between January 2012 and June 2014, a total of 1734 cirrhotic patients were enrolled and were classified into 'AUGIB' (n ¼ 497) and 'no AUGIB' (n ¼ 1237) groups according to their disease history. They were further divided into 'AEVB' (n ¼ 297) and 'no AEVB' (n ¼ 1259) groups according to the endoscopic findings. Additionally, 178 patients with AUGIB were not assigned to either the 'AEVB' or 'no AEVB' groups due to the absence of any endoscopic findings. Results: Compared with the 'no AUGIB' group, the 'AUGIB' group had similar PLT (99.99 6 89.90 vs.101.47 6 83.03; P ¼ 0.734) and APTT (42.96 6 15.20 vs.43.77 6 11.01; P ¼ 0.219), but significantly higher PT (17.30 6 5.62 vs.16.03 6 4.68; P < 0.001) and INR (1.45 6 0.69 vs.1.31 6 0.59; P < 0.001). A lower PT was independently associated with the absence of AUGIB (OR ¼ 0.968; 95% CI: 0.942-0.994). Compared with the 'no AEVB' group, the 'AEVB' group had significantly lower PLT (86.87 6 62.14 vs.101.74 6 83.62; P ¼ 0.004) and APTT (40.98 6 7.9 vs.43.72 6 10.97; P < 0.001), but similar PT (16.53 6 3.71 vs.16.04 6 4.68; P ¼ 0.088) and INR (1.35 6 0.41 vs.1.31 6 0.59; P ¼ 0.225). A higher PLT was independently associated with the absence of AEVB (OR ¼ 1.004; 95% CI: 1.002-1.006; P ¼ 0.001). Conclusio ns: PLT was associated with the occurrence of portal hypertension-related bleeding in liver cirrhosis.

Microcantilevers with embedded piezotransistors formulate simple and sensitive MEMS sensors. In this reported work, three different p-type metal-oxide-semiconductor field-effect transistor (PMOSFET) embedded microcantilevers are fabricated and their responses to physical displacements are evaluated. Effects of gate bias on the drain current change and device sensitivity are investigated. Specifically, a wide tuning range above 200% is demonstrated for the PMOSFET with the width/length ratio of 5 within a gate bias span of 6 V. Such tunable feature can be very useful to compensate process variations and optimise device performance for maximum sensitivity.

In this paper, we present a systematic characterization and modeling technique for the micromechanical free?free beam resonator to analyze its nonlinear vibration behavior. Different from the conventional FEM-based approach whose simulation accuracy is usually limited around 60?70%, the proposed modeling method is able to accurately identify both the mechanical and electrostatic nonlinear parameters from just a few preliminary experimental observations. The nonlinear equation of motion is then numerically solved, demonstrating both the spring hardening and softening effects in the system. The simulated nonlinear behavior of the resonator under different driving conditions is validated by comparing them with the experimental data. In addition, based on the verified nonlinear model, design guidelines such as the nonlinearity cancellation are also highlighted. Although this work focuses on the free?free beam resonators, the proposed modeling approach can be applied to any other electrostatically driven microresonator to reveal different intrinsic nonlinear properties of the device.

A report is presented, for the first time, on the effect of release etch holes on the quality factors of bulk-mode micromechanical resonators. The bulk resonators were operated in the Lame mode with frequencies around 6 MHz. Periodic 10 mum square etch holes with 30 mum spacing were placed at various locations on the surface of the resonator. A study on five such identical resonators with etch holes at various locations conclusively shows that etch holes decrease the quality factors by more than an order of magnitude from 1.67 million to 116 000 owing to two main energy loss mechanisms. Furthermore, it is demonstrated that the quality factor depends on the location of etch holes on the resonator.

An innovative gap reduction technique is reported to achieve sub-micron capacitive gaps for micromechanical resonators to boost the output signal using the standard low-cost 2 µm commercially available foundry process from MEMSCAP. Electrostatic actuation was used to reduce the gap size below the fabrication limitation. To demonstrate the proposed idea, a 6.35 MHz Lame-mode square resonator was designed, fabricated and tested. The resonator gap size was experimentally measured to be 0.64 µm, which boosted the resonance peak by 20 dB.