Regenerative failure of intrahepatic biliary cells in Alagille syndrome rescued by elevated Jagged/Notch/Sox9 signaling.

Despite the robust healing capacity of the liver, regenerative failure underlies numerous hepatic diseases, including the JAG1 haploinsufficient disorder, Alagille syndrome (ALGS). Cholestasis due to intrahepatic duct (IHD) paucity resolves in certain ALGS cases but fails in most with no clear mechanisms or therapeutic interventions. We find that modulating jag1b and jag2b allele dosage is sufficient to stratify these distinct outcomes, which can be either exacerbated or rescued with genetic manipulation of Notch signaling, demonstrating that perturbations of Jag/Notch signaling may be causal for the spectrum of ALGS liver severities. Although regenerating IHD cells proliferate, they remain clustered in mutants that fail to recover due to a blunted elevation of Notch signaling in the distal-most IHD cells. Increased Notch signaling is required for regenerating IHD cells to branch and segregate into the peripheral region of the growing liver, where biliary paucity is commonly observed in ALGS. Mosaic loss- and-gain-of-function analysis reveals Sox9b to be a key Notch transcriptional effector required cell autonomously to regulate these cellular dynamics during IHD regeneration. Treatment with a small-molecule putative Notch agonist stimulates Sox9 expression in ALGS patient fibroblasts and enhances hepatic sox9b expression, rescues IHD paucity and cholestasis, and increases survival in zebrafish mutants, thereby providing a proof-of-concept therapeutic avenue for this disorder.

Design and Implementation of an Event-Driven Smart Sensor Node for Wireless Monitoring Systems.

In this paper, an event-driven wireless sensor node is proposed and demonstrated. The primary design objective is to devise a wireless sensor node with miniaturization, integration, and high-accuracy recognition ability. The proposed wireless sensor node integrates two vibration-threshold-triggered energy harvesters that sense and power a threshold voltage control circuit for power management, a microcontroller unit (MCU) for system control, a one-dimensional convolutional neural network (1D-CNN) environment data analysis and vibration events distribution, and a radio frequency (RF) digital baseband transmitter with IEEE 802.15.4-/.6 protocols. The dimensions of the wireless sensor node are 4 × 2 × 1 cm3. Finally, the proposed wireless sensor node was fabricated and tested. The alarming time for detecting the vibration event is less than 6 s. The measured recognition accuracy of three events (knock, shake, and heat) is over 97.5%. The experimental results showed that the proposed integrated wireless sensor node is very suitable for wireless environmental monitoring systems.

[Imaging measurement and clinical significance of the angle between the axis of pedicle and the plane of lamina in lower cervical vertebra].

OBJECTIVE: To explore the imaging measurement and clinical significance of the angle between the axis of pedicle and the plane of lamina in lower cervical vertebra.
 Methods: Three dimensional reconstruction of CT scan was performed in 30 patients with cervical deformity, and the angle between the axis of pedicle and the plane of lamina was measured with the specific reconstructed CT image of C3-C7.
 Results: 1) The left and right transverse angle of C3-C7 between the axis of pedicle and the ipsilateral plane of lamina were 98.3°±6.3°, 98.0°±5.1°, 97.5°±6.9°, 95.1°±5.0°, 85.8°±5.4° and 96.7°±8.2°, 98.7°±7.1°, 97.8°±3.6°, 93.2°±6.2°, 86.8°±5.7°, respectively, which showed a gradual decreasing trend. Meanwhile the angle of C3-C6 was more than 90 degrees and C7 was less than 90 degrees. In addition to C6 with C3 and C7 with other segments, the rest of the differences between the sections was not statistically significant (all P>0.05). 2) The left and right transverse angle of C3-C7 between the axis of pedicle and the pedicle of vertebral arch of lamina were 0.2°±4.5°, 1.2°±7.2°, -0.8°±6.8°, -3.3°±5.4°, -14.7°±4.0° and -1.6°±5.4°, 1.9°±4.6°, -0.5°±6.0°, -4.6°±5.3°, -13.7°±3.4°, respectively, which showed a first increasing and then reducing trend. Meanwhile the angle of C4 was maximum angle. In addition to C6 with C3, C6 with C4, and C7 with other segments, the differences between the sections was not statistically significant (all P>0.05). 3) The left and right sagittal angle of C3-C7 between the axis of pedicle and the ipsilateral plane of lamina were 77.7°±7.6°, 77.0°±7.1°, 85.3°±8.4°, 94.1°±2.2°, 94.9°±3.8° and 78.5°±7.1°, 76.2°±6.2°, 86.4°±6.4°, 94.0°±2.7°, 95.6°±3.8°, respectively, which showed a gradual increasing trend. The angle of C3-C4 was less than 90 degrees. C5 showed large variation and C6-C7 was more than 90 degrees. In addition to C3 with C4 and C6 with C7, the differences between the sections was statistically significant (all P<0.05). There was no significant difference between the two sides of the above indexes (all P>0.05).
 Conclusion: In low cervical vertebra, there is a certain angle relationship between the axis of pedicle and the plane of lamina, which can provide reference for the clinical determination of angle of pedicle screw insertion.

Kemeny Constant-Based Optimization of Network Clustering Using Graph Neural Networks.

The recent trend in using network and graph structures to represent a variety of different data types has renewed interest in the graph partitioning (GP) problem. This interest stems from the need for general methods that can both efficiently identify network communities and reduce the dimensionality of large graphs while satisfying various application-specific criteria. Traditional clustering algorithms often struggle to capture the complex relationships within graphs and generalize to arbitrary clustering criteria. The emergence of graph neural networks (GNNs) as a powerful framework for learning representations of graph data provides new approaches to solving the problem. Previous work has shown GNNs to be capable of proposing partitionings using a variety of criteria. However, these approaches have not yet been extended to Markov chains or kinetic networks. These arise frequently in the study of molecular systems and are of particular interest to the biomolecular modeling community. In this work, we propose several GNN-based architectures to tackle the GP problem for Markov Chains described as kinetic networks. This approach aims to maximize the Kemeny constant, which is a variational quantity and it represents the sum of time scales of the system. We propose using an encoder-decoder architecture and show how simple GraphSAGE-based GNNs with linear layers can outperform much larger and more expressive attention-based models in this context. As a proof of concept, we first demonstrate the method's ability to cluster randomly connected graphs. We also use a linear chain architecture corresponding to a 1D free energy profile as our kinetic network. Subsequently, we demonstrate the effectiveness of our method through experiments on a data set derived from molecular dynamics. We compare the performance of our method to other partitioning techniques, such as PCCA+. We explore the importance of feature and hyperparameter selection and propose a general strategy for large-scale parallel training of GNNs for discovering optimal graph partitionings.

CX3CL1/CX3CR1 axis alleviates inflammation and apoptosis in human nucleus pulpous cells via M2 macrophage polarization.

CX3C chemokine ligand 1 (CX3CL1) belongs to the CX3C chemokine family and is involved in various disease processes. However, its role in intervertebral disc degeneration (IDD) remains to be elucidated. In the present study, western blotting, reverse transcription-quantitative PCR and ELISA assays were used to assess target gene expression. In addition, immunofluorescence and TUNEL staining were used to assess macrophage infiltration, monocyte migration and apoptosis. The present study aimed to reveal if and how CX3CL1 regulates IDD progression by exploring its effect on macrophage polarization and apoptosis of human nucleus pulposus cells (HNPCs). The data showed that CX3CL1 bound to CX3C motif chemokine receptor 1 (CX3CR1) promoted the M2 phenotype polarization via JAK2/STAT3 signaling, followed by increasing the secretion of anti-inflammatory cytokines from HNPCs. In addition, HNPC-derived CX3CL1 promoted M2 macrophage-derived C-C motif chemokine ligand 17 release thereby reducing the apoptosis of HNPCs. In clinic, the reduction of mRNA and protein levels CX3CL1 in degenerative nucleus pulposus tissues (NPs) was measured. Increased M1 macrophages and pro-inflammatory cytokines were found in NPs of IDD patients with low CX3CL1 expression. Collectively, these findings suggested that the CX3CL1/CX3CR1 axis alleviates IDD by reducing inflammation and apoptosis of HNPCs via macrophages. Therefore, targeting CX3CL1/CX3CR1 axis is expected to produce a new therapeutic approach for IDD.

Dissecting the genetic and microenvironmental factors of gastric tumorigenesis in mice.

Gastric cancer (GC) is one of the most frequent and lethal malignancies in the world. However, our understanding of the mechanisms underlying its initiation and progression is limited. Here, we generate a series of primary GC models in mice with genome-edited gastric organoids, which elucidate the genetic drivers for sequential transformation from dysplasia to well-differentiated and poorly differentiated GC. Further, we find that the orthotopic GC, but not the subcutaneous GC even with the same genetic drivers, display remote metastasis, suggesting critical roles of the microenvironment in GC metastasis. Through single-cell RNA-seq analyses and functional studies, we show that the interaction between fibronectin 1 on stomach-specific macrophages and integrin a6ß4 on GC cells promotes remote metastases. Taken together, our studies propose a strategy to model GC and dissect the genetic and microenvironmental factors driving the full-range gastric tumorigenesis.

Acquired semi-squamatization during chemotherapy suggests differentiation as a therapeutic strategy for bladder cancer.

Cisplatin-based chemotherapy remains the primary treatment for unresectable and metastatic muscle-invasive bladder cancers (MIBCs). However, tumors frequently develop chemoresistance. Here, we established a primary and orthotopic MIBC mouse model with gene-edited organoids to recapitulate the full course of chemotherapy in patients. We found that partial squamous differentiation, called semi-squamatization, is associated with acquired chemoresistance in both mice and human MIBCs. Multi-omics analyses showed that cathepsin H (CTSH) is correlated with chemoresistance and semi-squamatization. Cathepsin inhibition by E64 treatment induces full squamous differentiation and pyroptosis, and thus specifically restrains chemoresistant MIBCs. Mechanistically, E64 treatment activates the tumor necrosis factor pathway, which is required for the terminal differentiation and pyroptosis of chemoresistant MIBC cells. Our study revealed that semi-squamatization is a type of lineage plasticity associated with chemoresistance, suggesting that differentiation via targeting of CTSH is a potential therapeutic strategy for the treatment of chemoresistant MIBCs.

KMT2C deficiency promotes small cell lung cancer metastasis through DNMT3A-mediated epigenetic reprogramming.

Small cell lung cancer (SCLC) is notorious for its early and frequent metastases, which contribute to it as a recalcitrant malignancy. To understand the molecular mechanisms underlying SCLC metastasis, we generated SCLC mouse models with orthotopically transplanted genome-edited lung organoids and performed multiomics analyses. We found that a deficiency of KMT2C, a histone H3 lysine 4 methyltransferase frequently mutated in extensive-stage SCLC, promoted multiple-organ metastases in mice. Metastatic and KMT2C-deficient SCLC displayed both histone and DNA hypomethylation. Mechanistically, KMT2C directly regulated the expression of DNMT3A, a de novo DNA methyltransferase, through histone methylation. Forced DNMT3A expression restrained metastasis of KMT2C-deficient SCLC through repressing metastasis-promoting MEIS/HOX genes. Further, S-(5'-adenosyl)-L-methionine, the common cofactor of histone and DNA methyltransferases, inhibited SCLC metastasis. Thus, our study revealed a concerted epigenetic reprogramming of KMT2C- and DNMT3A-mediated histone and DNA hypomethylation underlying SCLC metastasis, which suggested a potential epigenetic therapeutic vulnerability.

Inflammatory response and oxidative stress attenuated by sulfiredoxin­1 in neuron­like cells depends on nuclear factor erythroid­2­related factor 2.

Sulfiredoxin­1 (SRX1) is a conserved endogenous antioxidative protein, which is involved in the response to cellular damage caused by oxidative stress. Oxidative stress and inflammation are the primary pathological changes in spinal cord injuries (SCI). The aim of present study was to explore the roles of SRX1 in SCI. Using reverse transcription­quantitative PCR and western blotting, the present study discovered that the expression levels of SRX1 were downregulated in the spinal cord tissues of SCI model rats. Massive irregular cavities and decreased Nissl bodies were observed in the model group compared with the sham group. Thus, to determine the underlying mechanisms, neuron­like PC12 cells were cultured in vitro. Western blotting analysis indicated that SRX1 expression levels were downregulated following the exposure of cells to lipopolysaccharide (LPS). Following the transfection with the SRX1 overexpression plasmid and stimulation with LPS, the results of the Cell Counting Kit­8 assay indicated that the cell viability was increased compared with LPS stimulation alone. Furthermore, the expression levels of proinflammatory cytokines secreted by LPS­treated PC12 cells were downregulated following SRX1 overexpression. Increased malondialdehyde content, decreased superoxide dismutase activity and reactive oxygen species production were also identified in PC12 cells treated with LPS using commercial detection kits, whereas the overexpression of SRX1 partially reversed the effects caused by LPS stimulation. The aforementioned results were further verified by determining the expression levels of antioxidative proteins using western blotting analysis. In addition, nuclear factor erythroid­2­related factor 2 (NRF2), a transcription factor known to regulate SRX1, was indicated to participate in the protective effect of SRX1 against oxidative stress. Inhibition of NRF2 further downregulated the expression levels of SRX1, NAD(P)H dehydrogenase quinone 1 and heme oxygenase­1 in the presence of LPS, while activation of NRF2 reversed the effects of LPS on the expression levels of these proteins. In conclusion, the results of the present study indicated that the anti­inflammatory and antioxidative effects of SRX1 may depend on NRF2, providing evidence that SRX1 may serve as a novel molecular target to exert a neuroprotective effect in SCI.

17ß-Estradiol Prevents Extracellular Matrix Degradation by Downregulating MMP3 Expression via PI3K/Akt/FOXO3 Pathway.

STUDY DESIGN: In vitro studies of the role of 17ß-estradiol (E2) and its possible targets in intervertebral disc degeneration (IDD). OBJECTIVE: To define the regulatory role of E2 in IDD and the potential mechanisms. SUMMARY OF BACKGROUND DATA: IDD has intricate etiology that is influenced by multiple risk factors. However, the underlying molecular mechanisms of occurrence and progression of IDD are not well elucidated. The degradation of extracellular matrix (ECM) has been extensively observed in IDD. E2 was found to inhibit ECM degradation in human nuleus pulposus cells (HNPCs), but the molecular mechanism remained to be determined. METHODS: Western blot and qPCR was performed to quantify the expression of target proteins in HNPCs. Luciferase reporter gene assay was applied to detect the effects of E2 and forkhead box O-3 (FOXO3) on matrix metalloproteinases (MMP)-3 promoter activity. Chromatin immunoprecipitation assay analyzed the binding of FOXO3 to MMP-3 and the effect of E2 on this process. RESULTS: We identified the upregulation of collagen II and aggrecan by E2 independent of time and concentration. And E2 downregulated MMP-3 expression in human nucleus pulposus cells. The phosphorylation of FOXO3 led to the reduction of MMP-3 promoter activity. Furthermore, 17ß-estradiol-induced the activation of PI3K/Akt pathway is required for FOXO3 phosphorylated. CONCLUSION: E2 prevents the degradation of ECM by upregulating collagen II and aggrecan expression via reducing MMP-3 expression in HNPCs, and PI3K/Akt/FOXO3 pathway is dispensable for MMP-3 downregulated. Therefore, E2 protects against IDD by preventing ECM degradation. LEVEL OF EVIDENCE: 3.

The Role of HER2 in Self-Renewal, Invasion, and Tumorigenicity of Gastric Cancer Stem Cells.

BACKGROUND: Deregulation of HER2 expression could affect the biological characteristics of gastric cancer cells and treatment option for gastric cancer patients. This research aims to investigate the impact of HER2 on biological characteristics of gastric cancer stem cells (GCSCs) and prognosis of gastric cancer patients. METHODS: HER2 knockdown in GCSCs were constructed by lentivirus transfection. Alterations of proliferation, self-renewal, invasion, migration, colony formation, and tumorigenicity of GCSCs were examined. The changes of gene expressions after HER2 interference in GCSCs were detected by gene microarray. The impact of concentration of serum HER2 and expression of HER2 in tumor tissues on survival of 213 gastric cancer patients was also analyzed. RESULTS: Down-regulation of HER2 decreased the self-renewal, colony formation, migration, invasion, proliferation, and chemotherapy resistance of GCSCs. However, the tumorigenicity of GCSCs in vivo was increased after down-regulation of HER2. The results of gene microarray showed that HER2 gene might regulate the signal transduction of mTOR, Jak-STAT, and other signal pathways and affect the biological characteristics of GCSCs. Furthermore, survival analyses indicated that patients with high concentration of HER2 in serum had a favorable overall survival. However, there was no significant correlation between expression of HER2 in tumor tissue and overall survival. CONCLUSION: Interference of HER2 in GCSCs decreased the capacity of self-renewal, proliferation, colony formation, chemotherapy resistance, invasion, and migration but might increase the tumorigenicity in vivo. Patients with high concentration of HER2 in serum seemed to have a favorable prognosis.

Investigations on pyrolysis of microalgae Diplosphaera sp. MM1 by TG-FTIR and Py-GC/MS: Products and kinetics.

In this work, pyrolysis characteristics and kinetics of microalgae Diplosphaera sp. MM1 cultivated in different mediums were investigated by TG-FTIR and Py-GC/MS. Harvested MM1s biomass varied with the changing in proximate and ultimate analyses presented different weight loss behaviors. The weight loss of MM1s cultivated in dairy and winery wastewater in main pyrolysis region was ~48.4 wt% and ~52.9 wt%, respectively, and both showed secondary weight loss after 570 °C. However, MM1 harvested from BG-11 medium exhibited maximum weight loss of ~63.5 wt% and no secondary weight loss. Further, the activation energies of MM1s harvested from dairy and winery wastewater (176.3 kJ/mol and 130.4 kJ/mol, respectively) were lower than that of BG-11medium (189.4 kJ/mol). The best mechanism function for MM1s pyrolysis was third-order f(α) = (1-α)3. Py-GC/MS results of MM1 cultivated in winery wastewater showed highest contents of C4-C10 and C11-C21 that characterized the carbon level of gasoline and diesel, respectively, which are the major components of bio-oils.

Clinical significance of putative markers of cancer stem cells in gastric cancer: A retrospective cohort study.

Cancer stem cells (CSCs) are thought as the source of tumor maintaining and many CSCs markers have been identified. Regarding the heterogeneity in gastric cancer (GC), TNM stage is not enough to accurately predict the prognosis. The aim of this study was to investigate the clinical significance of CSCs markers (Lgr5, Oct4, CD133, EpCAM, CD54 and Sox2) and establish a new model based on these markers to accurately predict prognosis of GC. We retrospectively enrolled 377 GC tissues from January 2006 to October 2012 to perform immunohistochemistry (IHC), and 93 pairs of GC tissues and corresponding adjacent normal gastric tissues to perform quantitative PCR (qPCR) from December 2011 to October 2012. The clinicopathological and follow-up characteristics were collected. In IHC, Oct4, CD133 and EpCAM were independently related to tumor progression, while Sox2 were associated with well or moderate differentiation (all p<0.05). Cox regression showed that Oct4-EpCAM was an independently prognostic factor, indicating that double low expression of Oct4-EpCAM group had significantly better prognosis than control group (p=0.035). Regarding qPCR, CD133 was an independent prognostic factor, showing that the prognosis of patients with CD133 high expression was significantly worse than that of patients with CD133 low expression (p<0.001). The prognostic prediction accuracy of nomogram based on Oct4-EpCAM expression in IHC was significantly better than TNM stage alone (p=0.003). Low expressions of Oct4-EpCAM in IHC and CD133 in qPCR were favorable prognostic factors in GC. The nomogram based on Oct4-EpCAM was valuable in prognostic prediction of GC patients.

The Value of Palliative Gastrectomy for Gastric Cancer Patients With Intraoperatively Proven Peritoneal Seeding.

The aim of this study was to evaluate the survival benefit of palliative gastrectomy for gastric cancer patients with peritoneal seeding proven intraoperatively and to identify positive predictive factors for improving survival.The value of palliative resection for gastric cancer patients with peritoneal metastasis is controversial.From 2006 to 2013, 267 gastric cancer patients with intraoperatively identified peritoneal dissemination were retrospectively analyzed. Patients were divided into resection group and nonresection group according to whether a palliative gastrectomy was performed. Clinicopathologic variables and survival were compared. Subgroup analyses stratified by clinicopathologic factors and multivariable analysis for overall survival were also performed.There were 114 patients in the resection group and 153 in nonresection group. The morbidities in the resection and nonresection groups were 14.91% and 5.88%, respectively (P = 0.014). There, however, was no difference in mortality between the 2 groups. The median survival time of patients in the resection group was longer than in nonresection group (14.00 versus 8.57 months, P = 0.000). The median survivals among the patients with different classifications of peritoneal metastasis were statistically significant (P = 0.000). Patients undergoing resection followed by chemotherapy had a significantly longer median survival, compared with that of patients who had chemotherapy alone, those who had resection alone, or those who had not received chemotherapy or resection (P = 0.000). Results of subgroup analyses showed that except for P3 patients and patients with multisite distant metastases, overall survival was significantly better in patients with palliative gastrectomy, compared with the nonresection group. In multivariate analysis, P3 disease (P = 0.000), absence of resection (P = 0.000), and lack of chemotherapy (P = 0.000) were identified as independently associated with poor survival.Palliative gastrectomy might be beneficial to the survival of gastric cancer patients with intraoperatively proven P1/P2 alone, rather than P3. Postoperative palliative chemotherapy could improve survival regardless of operation and should be recommended.

Comparisons Between Different Procedures of No. 10 Lymphadenectomy for Gastric Cancer Patients With Total Gastrectomy.

To compare the effectiveness and safety of in-vivo dissection procedure of No. 10 lymph nodes with those of ex-vivo dissection procedure for gastric cancer patients with total gastrectomy.Patients were divided into in-vivo group and ex-vivo group according to whether the dissection of No. 10 lymph nodes were performed after the mobilization of the pancreas and spleen, and migration out from peritoneal cavity. Clinicopathologic characteristics, overall survival, morbidity, and mortality were compared between the 2 groups.There were 148 patients in in-vivo group, while 30 in ex-vivo group. The baselines between the 2 groups were almost comparable. The metastatic ratio of No. 10 lymph nodes were 6.1% and 10.0% (P = 0.435) and the metastatic degree were 7.9% and 13.6% (P = 0.158) for in-vivo group and ex-vivo group, respectively. There was no difference in morbidity or mortality between the 2 groups. The number of total harvested lymph nodes and No. 10 lymph nodes increased significantly in ex-vivo group at the cost of prolonged operation time. The estimated overall survival rates for patients in in-vivo group and ex-vivo group were (3-year: 52.0% vs 61.8%) and (5-year: 45.3% vs 49.5%), respectively, without statistical significance. Further multivariable analysis had showed that the procedure of No. 10 lymphadenectomy was not a significant independent prognostic factor.Both in-vivo and ex-vivo dissection of No. 10 lymph nodes could be performed safely. It seems that ex-vivo dissection of No. 10 lymph nodes can result in a higher effective dissection at the cost of the operation time, but the overall survival rates were not statistically significant between the 2 groups, which should be confirmed further in a well-designed randomized controlled trial.

Tumor-Infiltrating Immune Cells Are Associated With Prognosis of Gastric Cancer.

Immune cells contribute to determining the prognosis of gastric cancer. However, their exact role is less clear. We determined the prognostic significance of different immune cells in intratumoral tissue (T), stromal tissue (S), and adjacent normal tissue (N) of 166 gastric cancer cases and their interactions, including CD3+, CD4+, CD8, CD57+, CD68+, CD66b+, and Foxp3+ cells, and established an effective prognostic nomogram based on the immune reactions. We found high densities of TCD3+, TCD4+, TCD8+, SCD3+, SCD4+, SCD57+, SCD66b+, and NFoxp3+ cells, as well as high TCD8+/SCD8+ ratio, TCD68+/SCD68+ ratio, TCD3+/TFoxp3+ ratio, TCD4+/TFoxp3+ ratio, TCD8+/TFoxp3+ ratio, SCD3+/SFoxp3+ ratio, and SCD4+/SCD8+ ratio were associated with better survival, whereas high densities of TCD66b+, TFoxp3+, SFoxp3+ and NCD66b+ cells as well as high TCD57+/SCD57+ ratio, TCD66b+/SCD66b+ ratio, SCD8+/SFoxp3+ ratio, and TFoxp3+/NFoxp3+ ratio were associated with significantly worse outcome. Multivariate analysis indicated that tumor size, longitudinal tumor location, N stage, TCD68+/SCD68+ ratio, TCD8+/TFoxp3+ ratio, density of TFoxp3+ cells, and TCD66b+/SCD66b+ ratio were independent prognostic factors, which were all selected into the nomogram. The calibration curve for likelihood of survival demonstrated favorable consistency between predictive value of the nomogram and actual observation. The C-index (0.83, 95% CI: 0.78 to 0.87) of our nomogram for predicting prognosis was significantly higher than that of TNM staging system (0.70). Collectively, high TCD68+/SCD68+ ratio and TCD8+/TFoxp3+ ratio were associated with improved overall survival, whereas high density of TFoxp3+ cells and TCD66b+/SCD66b+ ratio demonstrated poor overall survival, which are promising independent predictors for overall survival in gastric cancer.

Comparison of ultrasonic scalpel versus conventional techniques in open gastrectomy for gastric carcinoma patients: a systematic review and meta-analysis.

OBJECTIVES: To compare surgical efficacy and postoperative recovery of ultrasonic scalpel (USS) with conventional techniques for the resection of gastric carcinoma. METHODS: A systematic search of major medical databases (PubMed, Embase, CCRT and CNKI) was conducted. Both randomized and non-randomized controlled trials (RCTs and nRCTs) were considered eligible. Operation time (OT), intraoperative blood loss (BL) and postoperative complications (POC) rates as well as postoperative hospitalization days, number of dissected lymph nodes, abdominal drainage volume and time for recovery of gastrointestinal functions were synthesized and compared. RESULTS: Nineteen studies were included (7 RCTs and 12 nRCTs), in which 1930 patients were enrolled totally (946 in the USS group and 984 in the conventional group). Monopolar electrocautery and ligation were used as the conventional methods. Comparative meta-analysis showed perioperative outcomes were significantly improved using USS compared with conventional surgical instrumentation. OT was reduced from a weighted mean of 185.3 min in the conventional group to 151.0 min in the USS group (MD = -33.30, 95% CI [-41.75, -24.86], p<0.001) and intraoperative BL was decreased from a weighted mean of 217.9 ml in the conventional group to 111.6 ml in the USS group (MD = -113.42, 95% CI [-142.05, -84.79], p<0.001). Results from RCTs subgroup were consistent with those from nRCTs subgroup. The weighted cumulative risk of POC accounted for 8.9% (0%-25%) and 12.9% (5.5%-45%) in the USS and conventional groups, respectively. Pooled estimated results from nRCTs (OR = 0.54, 95% CI [0.27, 1.06], p = 0.07) and RCTs (RR = 0.75, 95% CI [0.44, 1.26], p = 0.27) showed no significant difference between the USS and control groups. Analysis of secondary outcomes showed the improvements of the USS group over control group regarding the number of dissected lymph nodes, postoperative hospitalization days, abdominal drainage volume and time for recovery of gastrointestinal functions. CONCLUSION: Compared with conventional electrosurgery, the USS is a safe and effective technique with more short-term advantages in open surgery for gastric cancer.