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There exist differences in the epidemiological characteristics, clinicopathological features, tumor biological characteristics, treatment patterns, and drug selections between gastric cancer patients from the Eastern and Western countries. The Chinese Society of Clinical Oncology (CSCO) has organized a panel of senior experts specializing in all sub‐specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually. Taking into account regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China. The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis, treatment, follow‐up, and screening of gastric cancer. Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines, this updated guideline integrates the results of major clinical studies from China and overseas for the past year, focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations. For the comprehensive treatment of non‐metastatic gastric cancer, attentions were paid to neoadjuvant treatment. The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated. For the comprehensive treatment of metastatic gastric cancer, recommendations for immunotherapy were included, and immune checkpoint inhibitors from third‐line to the first‐line of treatment for different patient groups with detailed notes are provided., The Chinese Society of Clinical Oncology (CSCO) organized a panel of senior experts specializing in all sub‐specialties of gastric cancer to compile the clinical guideline for gastric cancer in 2016 and then renewed it every year. The 2021 CSCO Clinical Practice Guidelines for gastric cancer covered the diagnosis, treatment, follow‐up and screening.

OBJECTIVE To investigate the potential mechanism of the effect of metabolic syndrome (MetS) on prostate volume (PV) and the risk of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and the relationships of MetS and the major pathogenic factors of MetS with the clinical progression of BPH/LUTS in older Chinese men. SUBJECTS AND METHODS We analyzed clinical data obtained from 506 ostensibly healthy men who underwent routine health check-ups and recruited 415 subjects from a group of previously studied men after 4 years. We evaluated the associations of major pathological factors of MetS, including insulin resistance, subclinical inflammatory state, and sex hormone changes, with PV, the risk of BPH and the clinical progression of BPH/LUTS by using multiple linear regression and logistic regression. RESULTS After adjustment for age, insulin, HOMA (homeostatic model assessment) index, leptin, resistin, adiponectin, C-reactive protein, tumor necrosis factor-α (TNF-α), sex hormone-binding globulin, and testosterone levels were significantly associated with PV (all P

The innovative and environmentally friendly methodologies for comprehensively enhancing the performances of high-strength steels without damage to plasticity, toughness and heat/corrosion/fatigue resistance are being developed. In recent years, nanoparticles elevate the field of high-strength steel. It is proposed that nanoparticles have the potential to replace conventional semi-coherent intermetallic compounds, carbides and alloying to optimize the steel. The fabrication process is simplified and the cost is lower compared with the traditional methods. Considerable research effort has been directed towards high-performance cast steels reinforced with nanoparticles due to potential application in major engineering. Nanoparticles are found to be capable of notably optimizing the nucleation behavior and precipitate process. The prominently optimized microstructure configuration and performances of cast steel can be acquired synchronously. In this review, the lattice matching and valence electron criterion between diverse nanoparticles and steel are summarized, and the existing various preparation methods are compared and analyzed. At present, there are four main methods to introduce nanoparticles into steel: external nanoparticle method, internal nanoparticle method, in-situ reaction method, and additive manufacturing method. These four methods have their own advantages and limitations, respectively. In this review, the synthesis, selection principle and strengthening mechanism of nanoparticles in cast steels for the above four methods are discussed in detail. Moreover, the main preparation methods and microstructure manipulation mechanism of the steel reinforced with different nanoparticles have been systematically expatiated. Finally, the development and future potential research directions of the application of nanoparticles in cast steel are prospected.

Immune checkpoint inhibitor (ICI)-associated myocarditis is a potentially fatal complication. Sparse published researches evaluated the prognostic value of cardiovascular magnetic resonance feature tracking (CMR-FT) for ICI-associated myocarditis.In the single-center retrospective study, 52 patients with ICI-associated myocarditis and CMR were included from August 2018 to July 2021. The ICI-associated myocarditis was diagnosed by using the clinical criteria of the European Society of Cardiology guidelines. Major adverse cardiovascular events (MACE) were comprised of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.During a median follow-up of 171 days, 14 (27%) patients developed MACE. For patients with MACE, the global circumferential strain (GCS), global radial strain (GRS), global longitudinal strain (GLS), and left ventricular ejection fraction (LVEF) were significantly worse and native T1 values and late gadolinium enhancement (LGE) extent were significantly increased, compared with patients without MACE (p0.05). The GLS remained the independent factor associated with a higher risk of MACE (hazard ratio (HR): 2.115; 95% confidence interval (CI): 1.379-3.246; p = 0.001) when adjusting for LVEF, LGE extent, age, sex, body mass index, steroid treatment, and prior cardiotoxic chemotherapy or radiation. After adjustment for LVEF, the GLS remained the independent risk factor associated with a higher rate of MACE among patients with a preserved LVEF (HR: 1.358; 95% CI: 1.007-1.830; p = 0.045).GLS could provide independent prognostic value over GCS, GRS, traditional CMR features, and clinical features in patients with ICI-associated myocarditis.• The global circumferential strain (GCS), global radial strain (GRS), and global longitudinal strain (GLS) by cardiovascular magnetic resonance feature tracking were significantly impaired in patients with an immune checkpoint inhibitor (ICI)-associated myocarditis. • GLS was still significantly impaired in patients with preserved left ventricular ejection fraction. • The worse GLS was an independent risk factor over GCS, GRS, traditional CMR features, and clinical features for predicting major adverse cardiovascular events in patients with ICI-associated myocarditis.

Sparse researches evaluated the quantitative cardiovascular magnetic resonance (CMR) parameters for immune checkpoint inhibitors (ICI)-associated myocarditis. We aimed to apply quantitative CMR mappings and late gadolinium enhancement (LGE) extent for detecting ICI-associated myocarditis.The retrospective study included patients with ICI-associated myocarditis and CMR examination from August 2018 to August 2021 in our hospital. ICI-associated myocarditis was clinically diagnosed based on the clinical criteria by European Society of Cardiology guidelines. The multiparametric CMR images including T2 mapping and black blood T2-weighted images were used to evaluate myocardial edema. The myocardial edema ratio (ER) ≥ 2.0 was applied for determining myocardial edema on T2-weighted images.56 patients with ICI-associated myocarditis were included. The global T2 value and native T1 value of patients with ICI-associated myocarditis were significantly higher than the reference ranges in our hospital (p 0.05). The rate of elevated global T2 value (92%) was significantly higher than those of abnormal native T1 value (73%), ER (52%) and LGE presence (68%) in patients with ICI-associated myocarditis (p 0.05). The LGE extent and left ventricular ejection fraction of patients with ICI-associated myocarditis were 10.38 ± 9.64% and 56.42 ± 8.54%, respectively. LGE extent inversely correlated with left ventricular ejection fraction (r = -0.38, p = 0.004) but positively correlated with native T1 value (r = 0.28, p 0.04) and extracellular volume (r = 0.50, p = 0.001).T2 mapping could detect higher rate of patients with ICI-associated myocarditis than native T1 mapping, ER and LGE presence. LGE extent inversely correlated with left ventricular ejection fraction but positively correlated with native T1 value and extracellular volume in patients with ICI-associated myocarditis.

Solute carrier family 25 (SLC25) encodes transport proteins at the inner mitochondrial membrane and functions as carriers for metabolites. Although SLC25 genetic variants correlate with human metabolic diseases, their roles in colon cancer remain unknown. Cases of colon cancer were retrieved from The Cancer Genome Atlas, and the transcriptionally differentially expressed members (DEMs) of SLC25 were identified. DNA level alterations, clinicopathological characteristics, and clinical survival were also investigated. A risk score model based on the DEMs was constructed to further evaluate their prognostic values in a clinical setting. The results were preliminarily validated using bioinformatic analysis of datasets from the Gene Expression Omnibus, immunohistochemical evaluations in clinical specimens, and functional experiments in colon cancer-derived cell lines. Thirty-seven DEMs were identified among 53 members of SLC25. Eight of 37 DEMs were introduced into a risk score model using integrated LASSO regression and multivariate Cox regression. Validated by GSE395282 and GSE175356, DEMs with high-risk scores were associated with the phenotypes of increasing tumor immune infiltration and decreasing glycolysis and apoptosis contents. SLC25A5 was downregulated in cancer, and its upregulation was related to better overall survival in patients from public datasets and in clinical cases. High SLC25A5 expression was an independent prognostic factor for 79 patients after surgical treatment. A negative correlation between CD8 and SLC25A5 was determined in specimens from 106 patients with advanced colon cancer. SLC25A5 attenuated cell proliferation, upregulated the expression of programmed cell death-related signatures, and exerted its biological function by inhibiting the MAPK signaling pathway. Our study reveals that mitochondrial SLC25 has prognostic value in patients with colon cancer. The bioinformatic analyses by following verification in situ and in vitro provide direction for further functional and mechanistic studies on the identified member of SLC25.

The Fukushima Accident happened 10 years ago. During the 10 years, the nuclear safety regulatory body of china takes some activities in non-reactor nuclear fuel cycle facilities, responding to the impact of the Fukushima accident. The activities include those review activities initiated immediately after the accident and those regulations revision activities. They will be presented in the present paper. The approaches for review, so called the safety reassessment, were firstly worked out. Those included a walk down with experts through the facility, the update of the external natural events, the review or revalidation of the design basis for the external natural events, the emergency preparedness and response for extreme natural disasters. According to the approaches, operating organizations implemented the safety reassessment to facilities which they operated and formed the result reports. The review results of those reports should be summarized into two points. The first point was that the information of the external natural events for each site was up-to-date, because new facilities continue to be built in the same site. The second point was the some building structures did not meet the requirements, because some standards were out of date, or updated. Meanwhile, the regulatory body thought that it was necessary to make a graded approach for different facilities. Finally, a rule was made. the graded approach also will be present in the paper.

In this paper, we took cold-rolled Al-Cu5.0-Mg0.5-Si0.5 alloy as the research object. The roles of 0.1 wt% in-situ nano-TiC and nano-TiC-TiB2 in solid–liquid and solid-state transformations (solution plus aging precipitation) were systematically investigated and compared. We found that trace in-situ nanoparticles can stimulate the nucleation of α-Al dendrites and hinder their growth, meanwhile serving as the heat storage and heat sustained-release carriers during solid–liquid transformation. In the process of solid-state transformation, recrystallization nucleation is promoted, and grain boundaries are pinned by nanoparticles. Meanwhile, the nucleation of Al2Cu is accelerated, and refined Al2Cu distributes more uniformly. Besides, similarities and differences in the manipulation mechanisms of nano-TiC and nano-TiC-TiB2 during solid–liquid and solid-state transformations were analyzed. The mechanical properties and the responsible strengthening mechanisms were discussed in detail.

Background: X-linked inhibitor of apoptosis (XIAP) is a vital factor in the anti-apoptosis mechanism of tumors and is highly expressed in renal cell carcinoma (RCC). However, the mechanism through which XIAP regulates DNA damage repair is unknown. This study investigated the regulatory mechanism of XIAP in etoposide-induced apoptosis in two Caki-1 cell lines with high or low XIAP expression. Methods: The two cell lines were established using RNA interference technology. The differentially expressed proteins in the two cell lines were globally analyzed through an isobaric tags for relative and absolute quantitation-based quantitative proteomics approach. Proteomic analysis revealed 255, 375, 362, and 5 differentially expressed proteins after 0, 0.5, 3, and 12 h of drug stimulation, respectively, between the two cell lines. The identified differentially expressed proteins were involved in numerous biological processes. In addition, the expression of histone proteins (H1.4, H2AX, H3.1, H3.2, and H3.3) was drastically altered, and the effects of XIAP silencing were accompanied by the marked downregulation of H2AX. Protein-protein interactions were assessed and confirmed through immunofluorescence and Western blot analyses. Results: The results suggested that XIAP may act as a vital cell signal regulator that regulates the expression of DNA repair-related proteins, such as H2AX, and influences the DNA repair process. Conclusions: Given these functions, XIAP may be the decisive factor in determining the sensitivity of RCC cell apoptosis induction in response to chemotherapeutic agents. Key words: Apoptosis; H2AX; iTRAQ; Renal cell carcinoma; X-linked inhibitor of apoptosis

This study aimed at the efficacy of sequential treatment of bone marrow-derived mesenchymal stem cell secretion for busulfan-treated azoospermia in mice. The conditioned media (CM) was obtained from bone marrow mesenchymal stem cells (MSCs) or 293 cells. Chemically induced azoospermia mice received 200 μl MSC-CM or 293-CM twice a week intravenously for three consecutive weeks. The histological assessment of spermatogenic recovery quantifying the expression of meiosis-associated genes, and Sertoli cell barrier functional factors were assessed. The characteristics of TM4 cells (Sertoli cell line) after pre-incubation of MSC-CM in vitro were also obtained. The MSC-CM group had the most spermatogenic colonies among the three groups (p < .05), but no spermatids were seen. Expressions of the meiosis-associated genes Dazl, Vasa, Miwi, Stra8, CyclinA1, Pgk2 and Scp3 in MSC-CM testis were remarkably higher compared with 293-CM and busulfan groups respectively (p < .05). The levels of Sertoli cell barrier functional factors, for example ICAM-1 and N-cadherin, were significantly increased during MSC-CM treatment (p < .05). Moreover, pre-incubation of MSC-CM particularly accelerated the CD54 (ICAM-1) and CD44 expressions of TM4 cells and promoted cell inherent adhesion. MSC-CM treatment can significantly improve the short-term restoration of spermatogonial structures of chemically induced azoospermia related to facilitating Sertoli cell adhesion integrity.

Total testosterone levels decline with age, while prostate volume and the prevalence of benign prostatic hyperplasia increase with age. We sought to investigate the correlation of serum testosterone levels with prostate volume in aging men. We analyzed clinical data obtained from 416 ostensibly healthy men who underwent routine health check-ups and recruited and collected data from these subjects 4 years later. We analyzed the correlation between prostate volume and relevant factors, as well as the correlation between changes in prostate volume and low testosterone over a 4-year period. Men with low testosterone had significantly larger prostate volume than those in the normal testosterone group (26.86 ± 8.75 vs. 24.06 ± 6.77 P = 0.02), and subjects with low testosterone had significantly higher levels of obesity-related factors, including waist circumference, body mass index, and insulin (all P P = 0.004), and prostate volume and 4-year changes in prostate volume were associated with low testosterone. With increased testosterone level, prostate volume showed a significant linear decreasing trend. These findings provide evidence of the relationship between testosterone and prostate volume. Additional large studies are needed to confirm these preliminary results.

BACKGROUND Genotyping of plasma cell-free DNA (cfDNA) is an increasingly important method to assess the tumor mutation status in colorectal cancer (CRC) patients. Clonal hematopoiesis (CH) releases non-tumor somatic mutations into blood, causing false positive results in cfDNA-based tumor genotyping. It is still not clear if CH should be examined in all CRC patients undergoing cfDNA analysis. METHODS We analyzed cfDNA KRAS, NRAS and BRAF genotypes in 236 metastatic CRC patients, who had matched tissue genotyping results, by next-generation sequencing using plasma cfDNA. The cfDNA-only mutations with allele frequencies (AFs) < 5% were highly suspicious for being CH-derived mutations. The origins of cfDNA mutations were confirmed by droplet digital polymerase chain reaction (ddPCR) using paired peripheral blood cells (PBCs) and CH-derived mutations were finally determined. One patient with a CH-derived mutation was followed up and the subpopulation of blood cells, in which CH was present, was investigated. RESULTS Three CH-derived mutations, KRAS Q61H, KRAS G12D and KRAS G12V, were identified in the patient cohort. All three patients harboring corresponding CH-derived mutations had a prior chemotherapy history. The CH-derived KRAS G12V mutation in a patient was found only present in lymphocytes and persisting under treatment. For all cfDNA mutations, the CH-derived ones were clustered in the patients with

PURPOSE: To evaluate the feasibility of dynamic contrast enhanced ultrasound (DCE-US) in predicting treatment response of high-intensity focused ultrasound (HIFU) in patients with locally advanced pancreatic cancer (LAPC) lesions. PATIENTS AND METHODS: In this prospective study, 10 patients with pathologically confirmed LAPC lesions (7 men, 3 women; average age, 61.13±5.80 years) were prospectively enrolled. All patients received HIFU treatment with peak intensity at 12000 W/cm2. Contrast enhanced ultrasound (CEUS) was performed with an ACUSON Oxana 2 ultrasound equipment and a 6 C-1 transducer (1–6 Hz). A dose of 2.4 ml SonoVue was injected for each examination. Time intensity curves (TICs) were generated and quantitative analyses were performed by SonoLiver software. B mode ultrasound (BMUS) features, CEUS enhancement patterns, TICs, CEUS quantitative parameters and serum carcinoma antigen 19-9 (CA19-9) levels were compared before and 4 weeks after HIFU treatment. Statistical analyses were performed with SPSS Version 20.0 and GraphPad Prism 5. RESULTS: While comparing before and after HIFU, no significant difference was obtained on mean size of lesion, BMUS or CEUS features. After HIFU treatment, TICs showed decreased and delayed enhancement. Among all CEUS quantitative parameters, significant decrease could be found in maximum intensity (MI) (60.66±23.95% vs 41.31±26.74%) and mean transit time (mTT) (76.66±47.61 s vs 38.42±28.35 s). CA19-9 level decreased significantly after HIFU (2747.92±4237.41 U/ml vs 715.08±1773.90 U/ml) (P = 0.05). CONCLUSION: DCE-US combining with quantitative analysis might be a useful imaging method for early treatment response evaluation of HIFU in LAPC lesions.

Gastric cancer (GC) is the second most common cancer in China. The ToGA study showed that trastuzumab in combination with fluoropyrimidine plus cisplatin prolonged overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced GC (AGC). However, some patients may not be able to receive this regimen. We conducted a clinical study to evaluate the efficacy and safety of trastuzumab in combination with docetaxel+capecitabine (DX) in patients with HER2-positive AGC. This phase II, multi-center, open-label, single arm study enrolled patients with HER2-positive AGC who had not received prior treatment for metastatic disease. Patients were treated with a regimen of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg, day 1), capecitabine (1000 mg/m(2) twice daily, days 1-14) and docetaxel (60 mg/m(2), day 1 for 6 cycles) every 3 weeks. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), OS and safety profiles. Sixty-seven patients with AGC were enrolled from 14 centers. 64 were included in the full analysis set (FAS). The median PFS was 8.1 months (95% confidence interval [CI]: 5.6-12.8) and the median OS was 20.9 months (95% CI: 15.1-33.0). Response was evaluated in 59 patients. The ORR was 67.8%. The most common adverse events of Grade ≥3 were neutropenia, leukopenia, hand-foot syndrome, febrile neutropenia and anemia. We concluded that combination treatment with trastuzumab and DX was well-tolerated and highly effective in patients with HER2-positive AGC, and may offer an alternative to current treatments.

To compare the efficacy of oxaliplatin-based and oxaliplatin-free adjuvant chemotherapies in patients with different Lauren type gastric cancers after D2 gastrectomy. From our established gastric cancer database, patients with pathological stage II and III gastric cancer who received adjuvant chemotherapy after D2 gastrectomy at Zhongshan Hospital of Fudan University were analyzed. Patients who received different adjuvant chemotherapy regimens were divided into two subgroups: oxaliplatin-based and oxaliplatin-free subgroup. Clinical outcomes were analyzed according to pathological stage and different Lauren types. From Jan 2010 to June 2017, a total of 580 patients met all the eligibility criteria and were enrolled. The median DFS for all the patients was 24.37 months and the median OS was 56.70 months. In patients with intestinal type gastric cancer, the median DFS of the oxaliplatin-based subgroup was significantly longer than that of oxaliplatin-free subgroup (48.73 vs. 18.33 months, P

Metal-ceramic composites generally exhibit limited strength-plasticity synergy due to pronounced difference in elastic and plastic deformation between “soft phase” and “hard phase”, bottlenecking their applications. This work proposes a novel microstructure design concept using refractory metals and intermetallics to offer compromises between “soft phase” and “hard phase”. A cost-effective fabrication method was used to produce 70 vol% (TiC + Al6MoTi + Mo)/Al cermet. The cermet is composed of submicron-TiC, micron-Al6MoTi and nano-Mo particles separated by Al in homogeneous microstructure. This multiple length-scale microstructure could delocalize stress concentration, enhance work hardening and deformation compatibility in cermet, resulting in unprecedentedly enhanced strength-plasticity synergy. Ultimate compressive strength, plastic strain and product of strength and plasticity of (TiC + Al6MoTi + Mo)/Al at room temperature and 573 K respectively are 1227 MPa, 6.9%, 7445 MPa·% and 781 MPa, 15.0%, 10021 MPa·%, which are increased by ~30%, ~25%, ~60% and ~37%, ~9%, 41% respectively compared with those for traditional 70 vol% TiC/Al. This work opens new perspectives for the design and application of metal-ceramic composites with high strength and plasticity synergy.

Background: Hepatocellular carcinoma (HCC) (about 85–90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. Summary: This guideline presents official recommendations of the National Health and Family Planning Commission of the People’s Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. Key Messages: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

Solution heat treatment (SHT), immediately followed by water quenching, can significantly improve the strength of precipitation-hardenable metallic materials, but frequently compromises the well-defined dimensional design of the geometrically complex or thin-wall engineering components. Here, to avoid this catastrophic high-temperature scheme, we introduce an alternative conceptual strategy to design a novel hypoeutectic Al–10Si–Mg alloy especially for “as-cast” services, i.e., extraordinarily high Mg addition and trace co-incorporation of innovative in situ TiCN–TiB2 particles coupled with a direct post-solidification isothermal low-temperature stabilization treatment (LTST). The performance was carefully characterized by multi-scale characterization techniques. Solidification kinetics and the resultant microstructural arrangement response to the TiCN–TiB2 particle additions were systematically investigated. Results demonstrated that both α-Al dendrites and eutectic Si structures were substantially refined by the TiCN–TiB2 particles. In the absence of conventional SHT, the precipitation kinetics associated with the customized LTST was also thoroughly studied. Interestingly, an extremely fine dispersion and high number density of perfectly coherent GP zones and pre-β'' nanoprecipitates were found coexisting after LTST. As a result, well-combined strength and ductility were therefore achieved by the synergistic effects of trace TiCN–TiB2 particles and LTST in this Al–10Si-2.0 Mg system.

The slab spatial composite effect arises due to compatible deformation of the reinforced concrete slab with the steel beam in composite frames. This effect can significantly amplify the stiffness of composite frame beams. Current Chinese design code adopts the stiffness amplification coefficient method for the design of composite frame beams, and the equivalent moment of inertia of the composite frame beam can be calculated to conduct the global analysis. However, the current formulae are only suitable for lateral load cases and symmetric I-shaped steel section. Therefore, this study aims to propose unified design equations of the stiffness amplification coefficient considering both vertical and lateral load cases and both symmetric and asymmetric I-shaped steel sections to address the aforementioned limitations. A series of parametric finite element analyses using the beam-shell mixed element model are conducted to derive the unified design equations. The reasonability of the proposed equations is verified by comparing the critical structural indices, such as the natural vibration period, inter-storey shear, lateral displacement, bending moment, and deflection distribution of numerical examples of multi-storey composite frames. Good accuracy is obtained through the comparison between the linear beam element model modified by the proposed equations and the beam-shell mixed element model.

Background Due to the phenotypic and molecular diversity of hepatocellular carcinomas (HCC), it is still a challenge to determine patients’ prognosis. We aim to identify new prognostic markers for resected HCC patients. Methods 274 patients were retrospectively identified and samples collected from Zhongshan hospital, Fudan University. We analyzed the gene expression patterns of tumors and compared expression patterns with patient survival times. We identified a “9-gene signature” associated with survival by using the coefficient and regression formula of multivariate Cox model. This molecular signature was then validated in three patients cohorts from internal cohort (n = 69), TCGA (n = 369) and GEO dataset (n = 80). Results We identified 9-gene signature consisting of ZC2HC1A, MARCKSL1, PTGS1, CDKN2B, CLEC10A, PRDX3, PRKCH, MPEG1 and LMO2. The 9-gene signature was used, combined with clinical parameters, to fit a multivariable Cox model to the training cohort (concordance index, ci = 0.85), which was successfully validated (ci = 0.86 for internal cohort; ci = 0.78 for in silico cohort). The signature showed improved performance compared with clinical parameters alone (ci = 0.70). Furthermore, the signature predicted patient prognosis than previous gene signatures more accurately. It was also used to stratify early-stage, HBV or HCV-infected patients into low and high-risk groups, leading to significant differences in survival in training and validation (P

The increase in strength usually accompanies by the sacrifice of ductility in the composites. This work proposed a strategy of design and synthesis of in-situ TiB2 particles to effectively tailor the microstructures and to enhance the mechanical performance of Al–Si-based composites. The tuning mechanisms for size and morphology of TiB2 particles were investigated by combustion synthesis in the Al–Ti–B reaction system. The nano/submicron-sized TiB2 particles with desirable morphology were then specially selected to construct high-performance Al–Si-based composites. Thanks to the strong interface bonding with a low crystallographic mismatch, TiB2 particles significantly refined the primary α-Al dendrites, eutectic Si and θ’ precipitates in the composites, which were 79.2%, 51.9% and 37.6% respectively smaller than those of the matrix. Numerical modeling results suggested that submicron-sized TiB2 particles were more likely to be engulfed or serve as heterogeneous sites while nano-sized TiB2 particles would be repulsed to the solid/liquid interface to physically restrict the growth of α-Al dendrites. The strength-ductility trade-off dilemma was broken therefore superior mechanical properties were obtained in the composites. This work provides a novel perspective for manipulating Al–Si-based alloys in terms of avoiding poisoning and achieving microstructural refinement and outstanding strength-ductility synergy.

The in situ TiC/Al-Cu nanocomposites were fabricated in the Al-Ti-C reaction systems with various carbon sources by the combined method of combustion synthesis, hot pressing, and hot extrusion. The carbon sources used in this paper were the pure C black, hybrid carbon source (50 wt.% C black + 50 wt.% CNTs) and pure CNTs. The average sizes of nano-TiC particles range from 67 nm to 239 nm. The TiC/Al-Cu nanocomposites fabricated by the hybrid carbon source showed more homogenously distributed nano-TiC particles, higher tensile strength and hardness, and better abrasive wear resistance than those of the nanocomposites fabricated by pure C black and pure CNTs. As the nano-TiC particles content increased, the tensile strength, hardness, and the abrasive wear resistance of the nanocomposites increased. The 30 vol.% TiC/Al-Cu nanocomposite fabricated by the hybrid carbon source showed the highest yield strength (531 MPa), tensile strength (656 MPa), hardness (331.2 HV), and the best abrasive wear resistance.

Efficient apoptosis requires Bcl-2 family-mediated mitochondrial outer membrane permeabilization (MOMP), which releases pro-apoptotic proteins to the cytosol, activating apoptosis and inhibiting X-linked inhibitor of apoptosis protein (XIAP). XIAP is a member of the inhibitors of apoptosis protein family whose expression is elevated in many cancer types and participates in the release of pro-apoptotic proteins. To explore the association between XIAP and the Bcl-2 family, and the influence of XIAP on mitochondria, RNA interference of XIAP was performed in Caki-1 cells and the dynamic change in the levels of related proteins was compared with the original Caki-1 cells upon induction of apoptosis. Upon knockdown of XIAP, the release of cytochrome c (Cyt-c), second mitochondria-derived activator of caspase (Smac) and apoptotic protease activating factor 1 (Apaf-1) from mitochondria proceeded normally, whereas in Caki-1 cells, the release of these pro-apoptotic proteins was significantly prolonged, and incomplete. Downregulation of XIAP through small interfering RNA resulted in an increase of apoptosis and a marked decrease in Bcl-2 and Bcl-xl levels at 3 h. Additionally, the regulation of the level of XIAP protein affected the specific ratios of Bcl-2/Bax and Bcl-xl/Bax, which play decisive roles in cell death. In the present study, it was revealed that XIAP can feed back to mitochondria, delaying Cyt-c and Apaf-1 release. Furthermore, XIAP can limit the release of its inhibitor Smac with the involvement of Bcl-2 family proteins.

The XELOX regimen (capecitabine plus oxaliplatin) has been demonstrated as first-line chemotherapy for gastric cancer in China. However, the efficacy of XELOX varies in individuals. Some evidences indicate that the variable efficacy might be related to the distinct immune status not only in the tumor site but also in the systemic immune system, and further investigation is required. In this study, we collected 32 PBMC samples from 16 XELOX-treated patients with gastric cancer and analyzed the patterns of immune cells. At the end point, the proportion of CD24(hi)CD27(+)CD19(+) B cells in patients without progression revealed a significant decrease compared with that in patients with progression, but not other immune cells, such as T cells and NK cells. Furthermore, CD19(+) B cells were more sensitive to capecitabine plus oxaliplatin stimulation in vitro than other immune cells, displaying higher frequency of apoptosis in a dose-dependent way. Thus, our results suggested that the outcomes of XELOX chemotherapy were inversely correlated with peripheral B cell subsets, which might provide a more convenient method to predict gastric cancer progression of XELOX-treated patients.

One paraffin block is routinely used for human epidermal growth factor receptor 2 (Her2/neu) immunohistochemistry (IHC) assessment. Here, we investigated if picking 2 paraffin blocks for Her2/neu evaluation on 1 slide is an economical, efficient, and practical method, which may reduce false negativity of Her2/neu IHC assessment due to intratumoral heterogeneity. A total of 251 gastric cancer (GC) patients were divided into a cohort using 1 tumor tissue paraffin block (single-block group, n = 132) and a cohort using dual tumor tissue paraffin blocks (dual-block group, n = 119) when evaluating Her2/neu expression status by IHC. In dual-block group, we combined the results from 2 different paraffin blocks and used the higher one as the final score. The number of IHC 1+, 2+, and 3+ specimens in the single-block group was 31 (23.5%), 40 (30.3%), and 19 (14.4%), respectively. The combined final IHC score in the dual-block group of 1+, 2+, and 3+ was 26 (21.8%), 34 (28.6%), and 23 (19.3%), respectively. Inconsistent Her2/neu expression between blocks was found in 36 (30.3%) cases in the dual-block group. The pooled data in the single-block group and the dual-block group indicated that, when using dual blocks, the Her2/neu-positive (3+) rate of GC was higher compared to that in the single-block group. Our results implied that using dual paraffin blocks to assess Her2/neu expression of GC may help identify more patients with Her2/neu-positive GC who could benefit from targeted therapy, by reducing false-negative rate of Her2 status assessment. This is an efficient, economical, and practical method for Her2/neu evaluation of GC.

Background: Due to the phenotypic and molecular diversity of hepatocellular carcinomas (HCC), it is a challenge to determine patients' prognosis. We aimed to identify new biomarkers of resected patients. Methods: We collected 274 HCC samples from patients at Zhongshan hospital, Fudan university. Gene expression analyses were performed using NanoString technology and compared with patient survival times. Using the coefficient and regression formula of the multivariate Cox model, we identified a "9-gene signature" associated with survival times. This molecular signature was then validated in three groups of patients from internal cohort (n=69), TCGA dataset (n=369) and HCC genomic consortium (n=80). Results: We identified 9-gene signature consisting of ZC2HC1A, MARCKSL1, PTGS1, CDKN2B, CLEC10A, PRDX3, PRKCH, MPEG1 and LMO2. The 9-gene signature was used, combined with clinical parameters, to fit a multivariable Cox model to the training data (concordance index, ci=0.85), which was successfully validated (ci=0.86 for internal cohort; ci=0.78 for external cohort). The signature showed improved performance compared with clinical parameters alone (ci=0.70). Furthermore, the signature more accurately predicted patient outcomes than gene signatures reported previously. It was also used to stratify early-stage, HBV or HCV-infected patients into groups with low and high risk of survival, leading to significant differences in survival in training and validation (P

Ni-coated SiCp/Al–Cu nanocomposites with different addition levels (0, 1, 2 and 3 wt% Ni-coated SiCp nanoparticulates) were successfully fabricated by semisolid stir casting combined with hot extrusion. The microstructures of the as-cast and hot-extruded nanocomposites showed that the grain size could be substantially refined. The dispersion mechanism of the SiCp nanoparticulates was discussed. Because the Al3Ni that was formed on the SiCp surface improved the wettability, more Ni-coated SiCp nanoparticulates were captured as the solid/liquid interface advanced, causing the Ni-coated SiCp to enter the α-Al interior and reduce agglomeration in the grain boundaries. The strengthening mechanism of the SiCp nanoparticulates at room temperature and high temperatures was studied. At 298 K, the strengthening was attributed to the hindrance of dislocation movement by the uniformly distributed SiCp nanoparticulates, grain size refinement and thermal mismatch strengthening. At 453 K and 493 K, the strengthening effect was ascribed to the impeded dislocation climb by the SiCp nanoparticulates distributed in the grain interior and the pinning effect of nanoparticulates on the grain boundaries.

The present study was designed to investigate the therapeutic effect of bone marrow MSC-derived factors on gonadotropic toxicity induced by busulfan in vivo. The conditioned media (CM) was obtained from MSCs in serum-free incubation for 48 hr and concentrated ~25-fold by ultrafiltration. The CM of HEK 293 cells was treated as control (293-CM). MSC-CM was injected into busulfan mice via caudal veins after 1 day of busulfan treatment for 2 weeks (200 μl per dose/twice weekly）. Compared to the 293-CM group, testicular injury was delayed in MSC-CM group, including reduced vacuolations of cells in the basal compartment of the seminiferous epithelium and detachment of cells from basement membrane. Apoptotic spermatogenic cells were significantly decreased in MSC-CM group (p ＜ 0.05). Interesting N-cadherin，ICAM-1 and P-cadherin expressions significantly increased in MSC-CM group, while occludin, ZO-1 and connexin 43 expressions showed no difference among MSC-CM, 293-CM and busulfan groups. Present results suggest MSC-secreted factors protect spermatogenesis impairment after busulfan treatment by reducing the apoptosis of spermatogenic cells and enhancing intercellular adhesion molecule expressions.