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The semi-solid slurry of 6061 aluminum alloy was prepared by the serpentine channel pouring process. The influence of graphite serpentine channel and copper serpentine channel on the slurry was comparative analyzed. The effect of pouring temperature on the slurry microstructure was also investigated. The results indicate that both copper and graphite serpentine channel can be used to prepare semi-solid slurry with spherical primary grains. Compared with a permanent casting, the microstructure of the semi-solid slurry was significantly improved and refined. With the increase of pouring temperature, the average equivalent grain diameter of the primary phase grains in the semi-solid slurry increases gradually, but the shape factor decreases gradually. When the pouring temperature increased from 675 °C to 690 °C, a high quality semi-solid slurry can be obtained. Comparing the two kinds of serpentine channel, it is found that the copper serpentine channel can make the primary grains finer, and the average equivalent grain size was 63 μm. However, the solidified shell near the inner graphite serpentine channel surface was thinner than that of the copper serpentine channel. In conclusion, the graphite serpentine channel is more suitable for preparing semi-solid 6061 aluminum alloy slurry.

Semi-solid 6061 aluminum alloy slurry was prepared by a graphite serpentine channel and its rheo-diecasting experiment was carried out on the slurry. The influence of pouring temperature on the microstructure evolution and mechanical properties of the rheo-diecasting were investigated. The microstructure and fracture mechanism of traditional die cast tensile specimens and rheo-diecast tensile specimens were compared and investigated. The results indicate that the microstructure of rheo-diecast tensile specimens is composed of spherical primary α-Al grains and fine secondary solidified α2-Al grains. When the pouring temperature increased from 660 °C to 720 °C, the average equivalent grain diameter of primary α-Al grains increased from 42 μm to 58 μm, and the shape factor decreased from 0.82 to 0.73. As the pouring temperature increases, the as-cast tensile strength and elongation of tensile specimens both increase first and then decrease. When the pouring temperature was 690 °C, the best mechanical properties were obtained, with as-cast tensile strength of 142.93 MPa and as-cast elongation of 4.86%. The fracture mechanism of traditional die casting is mainly ductile fracture, and the fracture mechanism of rheo-diecasting is a mixed fracture of intergranular fracture and ductile fracture.

The high-strength Al-Zn-Mg-Cu alloy has broad application prospects in high-end equipment manufacturing fields, such as aerospace, national defense and military industry, and transportation. However, the grains of Al-Zn-Mg-Cu alloy are coarse, and the grains further grow after heat treatment, which seriously reduces the mechanical property of alloy castings. Therefore, the study on reducing the grain size of the cast alloy was carried out by adding Zr element and applying electromagnetic stirring treatment technology, as well as suppressing the recrystallization of the aluminum alloy during the heat treatment process. The results show that adding Zr element reduced the grain size by 30%, the tensile strength increased by 50 MPa, and the elongation increased by more than 10%.

The cooling control of the melt during the casting process is of great significance. A comprehensive closed-loop cooling control of castings by adopting a skeletal sand mold design was proposed. The skeletal sand mold consisting of an adaptive shell, functional cavities and a support was designed and created based on the finite difference meshes of a casting. It was applied to a round wall test casting. Two kinds of skeletal sand molds, one with lattice support and the other with enforcing ribs for this casting were designed and printed out by the 3D printing (3DP) method. Aluminum alloy A356 was cast by using these two sand molds. The first mold was cooled by natural convection, the other one by water spray cooling. Two sound castings were obtained. The sand mold temperature, cooling curves, microstructures, mechanical properties, residual stress and deformation were measured, compared and discussed. Water spray cooling hastened the cooling rate by 62%, increased the content of Mg and Cu in the α-Al matrix, improved the mechanical properties, and altered the surface residual stress state.

High-strength aluminum alloy with large-scale and thin-walled complex castings have broad application prospects in aerospace, weapons, electronics, defense and military industries. However, due to the uneven thickness of the plate, the casting defects are inevitable by the ordinary casting method, and it is impossible to accurately control the shape and performance of the casting in the casting process. Previous studies have found that the semi-solid rheological extrusion casting technology with short process and near-end type can help solve this technical problem. Therefore, this paper studies the semi-solid rheological extrusion casting process of thin-walled complex casting of ZL114A aluminum alloy. The combination of numerical simulation and experimental research is used to simulate and optimize the filling and solidification process of thin-walled specimens. Based on this, a semi-solid rheological extrusion casting test was conducted. The result showed that, (1) The optimized model can well reflect the filling and solidification process under different rheological extrusion casting parameters, and obtain defect-free castings through process optimization. (2) The thin-walled parts of the thin plate casting produced by semi-solid rheology extrusion have excellent mechanical property and ductility.

Left thoracic approach (LTA) has been a favorable selection in surgical treatment for esophageal cancer (EC) patients in China before minimally invasive esophagectomy (MIE) is popular. This study aimed to demonstrate whether right thoracic approach (RTA) is superior to LTA in the surgical treatment of middle and lower thoracic esophageal squamous cell carcinoma (TESCC).Superiority clinical trial design was used for this multicenter randomized controlled two-parallel group study. Between April 2015 and December 2018, cT1b-3N0-1M0 TESCC patients from 14 centers were recruited and randomized by a central stratified block randomization program into LTA or RTA groups. All enrolled patients were followed up every three months after surgery. The software SPSS 20.0 and R 3.6.2. were used for statistical analysis. Efficacy and safety outcomes, 3-year overall survival (OS) and disease-free survival (DFS) were calculated and compared using the Kaplan-Meier method and the log-rank test.A total of 861 patients without suspected upper mediastinal lymph nodes (umLN) were finally enrolled in the study after 95 ineligible patients were excluded. 833 cases (98.7%) were successfully followed up until June 1, 2020. Esophagectomies were performed via LTA in 453 cases, and via RTA in 408 cases. Compared with the LTA group, the RTA group required longer operating time (274.48±78.92Esophagectomies via both LTA and RTA can achieve similar outcomes in middle or lower TESCC patients without suspected umLN. RTA is superior to LTA and recommended for the surgical treatment of more advanced stage TESCC due to more complete lymphadenectomy.ClinicalTrials.gov NCT02448979.

TPS488 Background: About 30.3-58.0% of patients who undergo esophagectomy may experience recurrence. The efficacy of postoperative chemoradiation has not been demonstrated in a randomized trial in patients with esophageal squamous cell carcinoma (ESCC) compared to surgery along. Therefore, it is urgent to explore more effective and safer postoperative regimen for resectable ESCC. Checkmate 577 has demonstrated immunotherapy can prolong disease free survival (DFS) for patients who have residual disease following preoperative chemoradiation and R0 resection. Anlotinib is an orally administered tyrosine kinase inhibitor that targets VEGFR1-3, FGFR1-4 and PDGFRα/β. In a randomized, double-blind phase 2 trial, the use of anlotinib in previously treated metastatic ESCC patients significantly improved progression-free survival (PFS) compared with placebo ( NCT02649361 ). TQB2450 is a novel humanized monoclonal antibody against PD-L1, which has shown encouraging activity in combination with anlotinib in the treatment of multiple tumors, such as biliary tract cancer (NCT03996408) and ovarian cancer (NCT04236362). The ALTER-E005 study is designed to evaluate the efficacy and safety of anlotinib combined with TQB2450as adjuvant therapy in ESCC patients. Methods: ALTER-E005 is a multi-center, single-arm, phase II study. A total of 30 patients will be enrolled. Eligible pts (≥18 years) must be histologically confirmed T1-2N1-3M0 or T3-4NanyM0 ESCC; received radical (R0) resection of ESCC with no recurrence in imaging examination within 6-12 weeks after surgery; ECOG PS 0–1. Patients enrolled will receive oral anlotinib 12 mg on days 1-14 and intravenous TQB2450 1,200 mg on day 1 every 3 weeks until disease recurrence. The primary endpoint is DFS. The secondary endpoints include safety, 1-year DFS rate, 3-year DFS rate, 1-year overall survival (OS) rate, and 3-year OS rate. Enrollment to the ALTER-E005 trial is currently ongoing in China. Clinical trial information: NCT05252078 .

In this paper, the effect of adding the refiner Sc to the high Zn/Mg ratio 7xxx series aluminum alloy melt on the hot tearing performance, microstructure, and mechanical properties of the alloy is studied. The hot tearing performance test (CRC) method is used to evaluate the hot tearing performance of the alloy. The squeeze casting process was used to form solid cylindrical parts to analyze the structure and properties of the alloy. This study shows that the hot cracking sensitivity of the alloy after the addition of the refiner Sc is significantly reduced. The ingot grain size is significantly reduced, and the average grain size is reduced from about 86 μm to about 53 μm. While the mechanical properties are significantly improved, and the tensile strength reduced from 552 MPa is increased to 571 MPa, and the elongation rate is increased from 11% to 14%.

PURPOSE: In contrast to other studies, our previous study showed that adding induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) significantly worsened the prognosis of patients with stage II nasopharyngeal carcinoma (NPC). However, the population used was small; therefore, there is an urgent need to confirm the result in a larger population because IC is still widely used in certain sections of china for stage II NPC. METHODS AND MATERIALS: We retrospectively analyzed an additional 272 patients. Therefore, in total, we report the results for 445 patients with stage II NPC treated with IC + CCRT or CCRT between June 2003 to June 2016 at the Zhejiang Cancer Hospital and Sun Yat-Sen University Cancer Center. RESULTS: This study included 445 patients treated with IC + CCRT (n = 195) or CCRT (n = 250). By last analysis, 22 (11.3%) patients in the IC + CCRT group developed local-regional recurrence and 23 (11.8%) patients developed distant metastases. Twenty-four (9.6%) patients in the CCRT group developed local-regional recurrence and 12 (4.8%) patients developed distant metastases. Univariate analyses showed that adding IC to CCRT significantly decreased the 5-year disease-free survival (DFS) (80.6% vs. 88.5%, P = .043); however, there was no statistically significant difference in 5-year overall survival (OS) (90.5% vs. 95.0%, P = .375). CONCLUSION: Using a larger population, the present study showed that adding IC to CCRT had a negative effect on patients with stage II NPC, which warrants further investigation.

Background The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented. Methods After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded. Results The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy. Conclusions TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC.

In this paper, the microstructure evolution of the rapidly solidified (RS) Mg61.7Zn34Gd4.3 (at%, atomic ratio) alloy at high temperatures was investigated. The hardness and elastic modulus of the main precipitated phases were also analyzed and compared with those of the α-Mg matrix on the basis of nanoindentation tests. The results show that the RS alloy consists of either a petal-like icosahedral quasicrystal (IQC) phase (~20 μm) and block-shaped H1 phase (~15 μm) or IQC particles with an average grain size of ~107 nm as well as a small proportion of amorphous phase, which mainly depends on the holding time at the liquid temperature and the thickness of the ribbons. The IQC phase gradually transforms at 400°C to a short-rod-shaped μ-phase (Mg28.6Zn63.8Gd7.7) with a hexagonal structure. The hardness of the IQC phase is higher than that of H1 phase, and both phases exhibit a higher hardness than the α-Mg matrix and the μ-phase. The elasticity of the H1 phase is superior to that of the α-Mg matrix. The IQC phase possesses a higher elastic modulus than H1 phase. The easily formed H1 phase exhibits the poorest plastic deformation capacity among these phases but a higher elastic modulus than the α-Mg matrix.

A semisolid slurry of 7075 aluminum alloy was prepared by means of a serpentine channel process (SCP) and rheo-diecasting. The influences of pouring temperature during slurry preparation, the injection pressure and die preheat temperature on the mechanical properties and microstructure of a rheo-diecast 7075 aluminum alloy were investigated. The results show that the as-cast strength and elongation of the tensile samples were 210-260 MPa and 0.2%-1.7%, respectively, with an injection pressure of 130 MPa, a pouring temperature of 700-720 ºC, a preheat temperature of 280-350 ºC, and a plunger speed of 0.5 m·s-1. The results also show that the aged strength and elongation of the tensile samples were 420-453 MPa and 1.0%-1.4%, respectively, when the alloy solution was treated at 470 ºC for 12 h and aged at 120 ºC for 24 h. The substantial shrinkage porosity in the 7075 aluminum alloy tensile samples was the main cause of low elongation.

The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival (DFS) of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with TKI, raising the necessity for further biomarker assessment. By comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers were identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC. Then we integrated them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorized patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.

The formation of the microstructure in the rheo-diecastings were studied by the experiment of rheo-diecasting with semi-solid A380 Aluminum alloy slurry. The results show that the grain diameter and shape factor of primary α-Al grains decreased and increased along the rheo-diecasting direction, respectively, making the primary α-Al grains gradually distributing uniformly. The combination of injection pressure and narrow gate of the runner and ingate was the main reason for the evolution of the primary α-Al grains, moreover, the collision and friction among primary α-Al grains during the filling were helpful for the refinement and spheroidization of the primary α-Al grains. The residual liquid solidified into the secondary solidification microstructure accompanied by the evolution of the primary α-Al grains. The accumulation of the fragments of the primary α-Al grains, the secondary α2-Al nuclei or grains which formed in previous positions, the effective nucleation rate of the residual liquid, and the collision and fraction among the secondary α2-Al grains and between the secondary α2-Al grain and the primary α-Al grains made the secondary solidification microstructure of the residual liquid present multiplex and complicate characteristics. In this paper, the formation of the microstructure in the rheo-diecastings were studied by the experiment of rheo-diecasting. During the rheo-diecasting, the grain diameter and shape factor of primary α-Al grains decreased and increased, respectively along the rheo-diecasting direction, which made the primary α-Al grains gradually distribute uniformly. The drifting of the fragments of the primary α-Al grains and secondary α2-Al nucleus, and the effective nucleation rate of the residual liquid played an important effect on the morphology of the secondary solidification structure.

Esophageal squamous cell carcinoma (ESCC) occurs at a relatively high frequency in China and is one of the most prevalent cancers in the world. Genome-wide association studies (GWAS) have identified 24 single-nucleotide polymorphisms (SNPs) that could be associated with ESCC in Chinese patients. This retrospective study aimed to validate the association between these 24 SNPs and ESCC in a Han Chinese subgroup from East China. A total of 2280 and 1900 patients with ESCC (case group) and non-esophageal cancer (control group) were included from a single center. Genotyping of the 24 polymorphisms was performed using the Sequenom MassARRAY system. Unconditional logistic regression analyses were conducted for every polymorphism. It was found that rs12188136 (P=0.027, OR=1.158, 95% CI=1.016-1.319 for AG/AA) was associated with ESCC. Binary logistic regression analyses revealed a significant negative association of rs875339 in RORA (P=0.014, OR=0.762, 95% CI=0.613-0.947 for TT/CC). Under the dominant model, rs6854472 was slightly associated with ESCC risk (P=0.048, OR=1.192, 95% CI=1.002-1.418). Under the recessive model, a significant negative association was observed for rs875339 (P=0.010, OR=0.758, 95% CI=0.615-0.935). In a word, this large-scale replication study validated that rs12188136 and rs6854472 are associated with ESCC in a Han Chinese subgroup from Eastern China, and that rs875339 is negative associated with ESCC.

The semisolid slurry of Al-Zn-Mg-Cu alloy was prepared through a self-designed water-cooled copper serpentine pouring channel (WSPC) machine. Influences of pouring temperature, the number of turns and the cooling water flow rate on the microstructure of the semisolid Al-Zn-Mg-Cu alloy slurry were investigated. The results show that the semisolid Al-Zn-Mg-Cu alloy slurry with satisfactory quality can be generated by the WSPC when the pouring temperature is in the range between 680 ºC and 700 ºC. At a given pouring temperature, the average grain size of primary α-Al decreases and the shape factor increases with the increase of the number of turns. When the cooling water flow rate is 450 L·h-1, the obtained semisolid slurry is optimal. During the preparation of the semisolid Al-Zn-Mg-Cu alloy slurry with low superheat pouring, the alloy melt has mixed inhibition and convection flow characteristics by “self-stirring”. When the alloy melt flows through the serpentine channel, the chilling effect of the inner wall of the channel, the convection and mixed inhibition of the alloy melt greatly promote the heterogeneous nucleation and grain segregation. This effect destroys the dendrite growth mode under traditional solidification conditions, and the primary nuclei gradually evolve into spherical or near-spherical grains.

s: The semi-solid slurry of Al-25%Si hypereutectic aluminum alloy was prepared through a copper serpentine pouring channel, the effect of pouring temperature and numbers of channel bend on the slurry microstructure was investigated. The results show that the primary silicon grains in Al-25%Si hypereutectic alloy solidified at a traditional condition are very large and the average silicon grain size is about 65.3μm, however, when the liquid Al-25%Si alloy is poured through a copper serpentine pouring channel, the primary silicon grains are fined obviously. If the channel has three bends and the pouring temperature is 747°C,the average silicon grain size in the slurry is about 33.7μm. If the channel has four bends and the pouring temperature is 747°C, the average silicon grain size in the slurry is about 30.9μm. If the channel has seven bends and the pouring temperature is 747°C, the average silicon grain size in the slurry is about 28.6μm. The analysis shows that the chilling effect of the inner channel wall precipitates primary silicon nuclei, and so the primary silicon grains of Al-25%Si alloy are fined greatly. Meanwhile, the subsequent washing of the alloy melt also promotes the separation of primary silicon grains from the inner wall and the primary silicon grains are further fined. The above research work demonstrates eventually that the copper serpentine pouring channel process is a good method for fining the primary silicon grains in hypereutectic Al-25%Si alloy rather than using chemical fining agent phosphorus as in traditional process.

In order to study the possibility of refining the primary silicon grains in the microstructure of hypereutectic Al-Si alloy through a serpentine pouring channel, the semi-solid slurry of A390 aluminum alloy was prepared through a water-cooled copper serpentine pouring channel, which is a new method proposed recently for semi-solid forming process, and the effect of pouring temperature on the slurry microstructure was investigated. The results show that the slurry of A390 aluminum alloy with refined primary silicon grains can be prepared under given conditions and especially when the pouring temperatures is 690°C, the primary silicon grains can be refined obviously, the equivalent silicon grain size is 19.7mm and the average shape factor is about 0.7. The analysis shows that the chilling effect of the inner channel wall precipitates a large number of primary silicon nuclei, and so the primary silicon grains are refined greatly. Meanwhile, the subsequent alloy melt washing also promotes the separation of primary silicon grains from the inner wall and the primary silicon grains are further refined. The work undertaken demonstrates eventually that the serpentine pouring channel process is a good method for refining the primary silicon grains in hypereutectic A390 alloy rather than using chemical fining agent phosphorus as in traditional process, and provides an alternative process choice.

Summary Background Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II–IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB–IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II–IIIA (N1–N2) NSCLC. Methods We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18–75 years with completely resected (R0), stage II–IIIA (N1–N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m 2 on days 1 and 8) plus intravenous cisplatin (75 mg/m 2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079. Findings Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8–44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months [95% CI 24·9–32·5]) than with vinorelbine plus cisplatin (18·0 months [13·6–22·3]; hazard ratio [HR] 0·60, 95% CI 0·42–0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two [2%] patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 [34%] patients vs none with gefitinib), leucopenia (14 [16%] vs none), and vomiting (eight [9%] vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related. Interpretation Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II–IIIA (N1–N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature. Funding Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China.

In this study, a series of Al-Zn-Mg-Cu alloy with different compositions added with Zr and Sc refiners are designed. The effect of main alloying elements (Zn, Mg, and Cu) on the grain structure, hot tearing performance, and mechanical properties of the alloy were investigated. It was found that as the content of alloying elements increases, the grain size becomes finer, the grain morphology changes from equiaxed crystal to fine dendrite, and the eutectic phase increase. The maximum and minimum hot tearing susceptibilities of the alloy occur for Zn in 9 and 5%. The hot tearing sensitivity of the alloy is greatly affected by the latent heat of the alloy, the viscosity, and the surface tension of the alloy. The alloying feeding performance is good because of the high content of the non-equilibrium eutectic phase while the alloying content is high. It could be concluded that the mechanical property of the alloy increases while the elongation decreases significantly as the content of alloying element increases. When the Zn content exceeds about 9%, a lot of non-equilibrium eutectic phase remains after heat treatment that resulting in a decrease in the strength and elongation of the alloy.

The variant selection of martensites (e-M and α′-M) and e-M reversion in dynamic tensile high-manganese TRIP steel were investigated. α′-M variant pairs with a zigzag morphology frequently formed, and the pairs of neighboring α′-M variants were examined in terms of mechanical work and strain energy reduction. The occurrence of a primary α′-M variant is determined by mechanical work, but high products of mechanical work and strain energy reduction are essential for secondary variant selection. In contrast to α′-M variant pair selection, e-M variant selection can be attributed to the highest mechanical work. During e-M→α′-M transformation, the mechanical work of e-M reversion is higher than that of α′-M variant, thereby implying that e-M reversion in 〈110〉 γ grain is possible. e-M plate distribution also affects the feasibility of e-M reversion.

The effects of pouring temperature, vibration frequency, and the number of curves in a serpentine channel, on the microstructure and mechanical properties of Al–30%Si alloy processed by rheo-diecasting (RDC) were investigated. The semisolid Al–30%Si alloy slurry was prepared by vibration serpentine channel pouring (VSCP) process in the RDC process. The results show that the pouring temperature, the vibration frequency, and the number of the curves strongly affect the microstructure and mechanical properties of Al–30%Si alloy. Under experimental conditions of a pouring temperature of 850 °C, a twelve-curve copper channel and a vibration frequency of 80 Hz, the primary Si grains are refined into fine compact grains with average grain size of about 24.6 μm in the RDC samples assisted with VSCP. Moreover, the ultimate tensile strength (UTS), elongation and hardness of the RDC sample are 296 MPa, 0.87% and HB 155, respectively. It is concluded that the VSCP process can effectively refine the primary Si grains. The refinement of primary Si grains is the major cause for the improvement of the mechanical properties of the RDC sample.

Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1–E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28. The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer., Oesophageal squamous-cell carcinoma (ESCC) is a leading cause of cancer death, and half of ESCC cases occur in China. Here, the authors provide an in depth genomic landscape for this disease and identify specific mutation signatures—one of which is linked to alcohol intake.

The semi-solid A380 aluminum alloy slurry prepared by water-cooling serpentine channel and its rheo-diecasting were studied in this paper. The result showed that the pouring temperature and cooling water flow rate had a significant effect on the semi-solid slurry. When the pouring temperature decreased from 670 to 610 °C, the average grain diameter and shape factor of the primary α-Al grains decreased from 64 to 47 µm and increased from 0.74 to 0.82, respectively, but the mass of semi-solid slurry blocked in channel increased. With the cooling water flow rate increasing from 0 to 1000 L/h, the semi-solid slurry firstly got optimized and then deteriorated. Under the condition of the same die casting process parameters, the rheo-diecastings produced by the semi-solid slurry prepared through water-cooled serpentine channel had higher mechanical properties than those of the traditional die castings. In this work, a new simple and low cost preparation of semi-solid slurry was invited, which was suitable for rheological forming of the short process. What's more, the rheo-diecasting was studied through comparing the traditional die casting. The result showed that the pouring temperature and cooling water flow rate had a significant effect on the semi-solid slurry. When the pouring temperature decreased, the average grain diameter and shape factor of the primary α-Al grains increased and decreased respectively. With the cooling water flow rate increasing, the semi-solid slurry firstly got optimized and then deteriorated. Under the condition of the same die casting process parameters, the rheo-diecastings produced by the semi-solid slurry prepared through water-cooled serpentine channel had higher mechanical properties than those of the traditional die castings.

Background: The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival (DFS) of resected EGFR-mutated stage II-IIIA non-small cell lung cancer (NSCLC). However, inconsistent clinical benefits have necessitated precise genetic categorization to reevaluate the benefit and risk assessment. Methods: Total 171 baseline surgical specimens from the ADJUVANT trial (n=95, gefitinib arm; n=76, VP arm) underwent targeted sequencing of 422 cancer-related genes. Predictive biomarkers of DFS were identified by Cox proportional hazard regression with gene-by-treatment interactions. A multi-gene composite score, MINERVA (Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies), that incorporates the predictive value of selected biomarkers, was developed for survival stratification based on the ratio of 2-year DFS rate and the difference in median DFS. The model was internally validated using ten-fold and leave-one-out cross-validation methods. Findings: TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC were identified as significant predictors for DFS and integrated into MINERVA score. Although updated overall OS presented no difference between adjuvant TKI and chemotherapy, MINERVA categorized patients into three subgroups. In Highly TKI-Preferable group (n=60, 35%), gefitinib achieved significantly longer median DFS than chemotherapy (34.5 vs 9.1 months; hazard ratio (HR) 0.21; p

To assess the benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as neoadjuvant/adjuvant therapies in locally advancedThis was a multicenter (17 centers in China), open-label, phase II, randomized controlled trial of erlotinib versus gemcitabine plus cisplatin (GC chemotherapy) as neoadjuvant/adjuvant therapy in patients with stage IIIA-N2 non-small-cell lung cancer withOf 386 patients screened, 72 were randomly assigned to treatment (intention-to-treat population), and 71 were included in the safety analysis (one patient withdrew before treatment). The ORR for neoadjuvant erlotinib versus GC chemotherapy was 54.1% versus 34.3% (odds ratio, 2.26; 95% CI, 0.87 to 5.84;The primary end point of ORR with 42 days of neoadjuvant erlotinib was not met, but the secondary end point PFS was significantly improved.

In this paper, the effects of rheo-diecast process parameters and T6 heat treatment on the microstructure and mechanical properties of the rheo-diecasting (RDC) semi-solid A390 alloy prepared through pure copper serpentine channel were investigated. The results indicate that the mechanical properties of the RDC samples change with the pouring temperature and injection pressure. In this case, a lower pouring temperature results in better tensile strength and elongation of the RDC A390 alloy; however, the tensile strength and elongation decrease when the pouring temperature decreases to 660°C. Higher injection pressures result in the improved mechanical properties of the RDC A390 alloy. To some extent, T6 heat treatment improves the tensile strength and ductility of the RDC A390 alloy compared to those of the non-heat treated alloy. However, when the pouring temperature and injection pressure are greater than 670°C and 70 MPa, respectively, the mechanical properties are sharply diminished.

The apparent viscosities of the semi-solid SiCp/A357 composites with 0vol.%, 10vol.% and 20vol.% SiC particles manufactured by stir casting were investigated using a Couette type viscometer, and the composite fluidity was examined with a test casting. The results showed that, the viscosities of the semi-solid SiCp/A357 composites decreased with an increase in shear rate, but increased with the increasing of solid fraction, and apparent viscosity of 10vol.% SiCp/A357 composite was the lower than that of 20vol.% SiCp/A357 composite at the same solid fraction; and the composite fluidity results were in a good agreement with the viscosity ones.

Ribonucleotide reductase M1 (RRM1) is a crucial gene in DNA repair. Recent studies have shown that RRM1 expression can be a powerful predictor of survival or chemotherapy sensitivity in patients presenting with carcinomas who are treated with adjuvant gemcitabine‐based chemotherapy including lung cancer. However, the relationship between the single nucleotide polymorphisms (SNP) of RRM1 and the susceptibility of lung cancer to chemotherapy has not been well addressed. We detected six tag SNPs of RRM1 genotypes in a cohort of 1007 patients with primary lung cancer and 1007 age‐ and sex‐matched population controls using SNaPshot detection technology. Logistic regression, odds ratios (OR), and 95% confidence intervals were calculated to estimate lung cancer risk associated with SNP genotypes and haplotypes, after adjusting for case–control matching factors. Compared with the T/T and A/T genotype of RRM1 *151A>T, the A/A genotype had an increased risk for overall lung cancer (adjusted OR, 1.33). Additionally, the T/T+T/C genotypes of RRM1 ‐756T>C were risk factors that increased the susceptibility to lung cancer (adjusted OR 1.54, as compared with the C/C genotype). While the T/T+G/T genotypes of RRM1 ‐585T>G behaved as protective factors to increase the susceptibility to lung cancer (adjusted OR 0.44, as compared with the C/C genotype). In summary, this is the first study to systematically identify the relationship between the polymorphisms of RRM1 and individual susceptibility to lung cancer. It is anticipated that the RRM1 *151A>T, RRM1 ‐756T>C, and RRM1 ‐585T>G polymorphisms will improve the predictive prognosis of lung cancer sensitivity.

In this study, a serpentine channel pouring process was used to prepare the semi-solid Al–20%Si alloy slurry and refine primary Si grains in the alloy. The effects of the pouring temperature, number of curves in the serpentine channel, and material of the serpentine channel on the size of primary Si grains in the semi-solid Al–20%Si alloy slurry were investigated. The results showed that the pouring temperature, number of the curves, and material of the channel strongly affected the size and distribution of the primary Si grains. The pouring temperature exerted the strongest effect, followed by the number of the curves and then the material of the channel. Under experimental conditions of a four-curve copper channel and a pouring temperature of 701°C, primary Si grains in the semi-solid Al–20%Si alloy slurry were refined to the greatest extent, and the lath-like grains were changed into granular grains. Moreover, the equivalent grain diameter and the average shape coefficient of primary Si grains in the satisfactory semi-solid Al–20%Si alloy slurry were 24.4 μm and 0.89, respectively. Finally, the refinement mechanism and distribution rule of primary Si grains in the slurry prepared through the serpentine channel pouring process were analyzed and discussed.

This study presents a modified annular electromagnetic stirring (M-AEMS) melt treatment suitable for a large-volume and high-alloyed aluminum alloy. A 3D computational model coupling an electromagnetic model with a macroscopic heat and fluid-flow model was established by using Ansoft Maxwell 3D and Fluent from ANSYS workbench, and the effects of the electromagnetic shielding ring, the height of the magnet yoke, the shape of the iron core, and the internal cooling mandrel on the electromagnetic, thermal and flow fields were studied numerically. Based on the optimal technical parameters, the effectivity of the M-AEMS process by using 7075 alloy was validated experimentally. The results show that a favorable electromagnetic field distribution can be achieved by changing the magnet yoke height, the iron-core shape and the electromagnetic shielding ring, and the melt temperature of the 7075 alloy can drop rapidly to the pouring temperature by imposing the internal cooling mandrel, compared with ordinary annular electromagnetic stirring, the M-AEMS process creates a lower magnetic strength near the melt top, beneficial for stabilizing the melt surface, meanwhile, it yields a higher magnetic strength near the melt bottom, which increases the shear rate and ensures an optimal stirring effect. Therefore, M-AEMS works more efficiently because the thermal and composition fields become uniform in a shorter time, which reduces the average grain size and the composition segregation, and a more stable melt surface can be obtained during treatment, which reduces the number of air and oxide inclusions in the melt.

The notable clinical success of cancer immunotherapy using checkpoint blockade suggests that it is likely to form the foundation of curative therapy for many malignancies. However, checkpoint blockades do not achieve sustained clinical response in most patients and thus amounts of problems needed to be figured out. Regarding these challenges, the 2017 Chinese Lung Cancer Summit expert panel organized a forum on the 14th Chinese Lung Cancer Summit to formally discuss these controversies. Five consensuses finally were reached to guide the application of checkpoint blockades.

By rolling and nitriding processes, 0.23- to 0.3-mm-thick grain-oriented 6.5 wt% silicon steel sheets were produced. The core losses of grain-oriented 6.5 wt% silicon steel at frequencies ranging from 400 Hz to 20 kHz were lower than that of the grain-oriented 3 wt% silicon steel with the same thickness by 16.6–35.8%. The secondary recrystallization behavior was investigated by scanning electron microscopy, energy-dispersive spectroscopy, and electron backscattered diffraction. The results show that the secondary recrystallization in high-silicon steel sheets develops more completely as the nitrogen content increases after nitriding, secondary recrystallized grain sizes become larger, and the sharpness of Goss texture increases. Because more $$\left\{ {110} \right\}\left\langle {116} \right\rangle$$ grains in the subsurface and the central layer of the sheets have a lot of 20°–45° high-energy boundaries in addition to Goss grains, $$\left\{ {110} \right\}\left\langle {116} \right\rangle$$ can be the main component through selective growth during secondary recrystallization when the inhibitor quantity is not enough and inhibitor intensity is weaker. The increases in nitrogen content can increase the inhibitor intensity and hinder abnormal growth of a mount of $$\left\{ {110} \right\}\left\langle {116} \right\rangle$$ grains and therefore enhance the sharpness of Goss texture.

Alterations of the epidermal growth factor receptor (EGFR), including overexpression or gene mutations, contribute to the malignant transformation of human epithelial cells. The aim of this study was to assess EGFR overexpression or gene amplification in esophageal squamous cell carcinoma (ESCC) tissue samples and investigate their correlations with biological behaviors. Tissue specimens from 56 patients with surgically resected ESCC were obtained for immunohistochemical analysis of EGFR expression and fluorescence in situ hybridization analysis of EGFR amplification. The data were statistically analyzed to determine the associations with patient clinicopathological and survival data. EGFR was overexpressed in 30 of the 56 (53.6%) ESCC samples and was associated with poor tumor differentiation (P=0.047). EGFR amplification was detected in 13 cases (23.2%) and was associated with advanced pathological stage (P=0.042) and tumor lymph node metastasis (P=0.002). The univariate analysis identified no association between EGFR overexpression and the overall survival (OS) of the patients. By contrast, EGFR amplification predicted ESCC prognosis (P=0.031), while the multivariate analysis revealed a marginal statistical significance for the association between EGFR amplification and OS (P=0.056). EGFR overexpression and increased EGFR copy number were common events in ESCC and contributed to malignant biological behaviors, including tumor dedifferentiation and lymph node metastasis. EGFR amplification may therefore be useful in predicting OS in patients with ESCC.

The semi-solid slurry of A380 aluminum alloy was prepared by the serpentine channel. The effects of pouring temperature, curve number and curve diameter of the serpentine channel on the microstructure of the semi-solid A380 aluminum alloy slurry were investigated. The results show that the satisfactory semi-solid A380 aluminum alloy slurry could be obtained when the pouring temperature ranged from 630 to 650 °C. Under the same conditions, increasing the curve number or reducing the curve diameter of the serpentine channel would decrease the average diameter and increase the shape factor of the primary α (Al) grains. The “self-stirring” of the alloy melt in the serpentine channel was beneficial to the ripening of the dendrites and the spheroidizing of the primary α (Al) grains.

Long noncoding RNAs (lncRNAs) are emerging as key regulators in various biological processes. Epithelial-to-mesenchymal transition (EMT) is a developmental process hijacked by tumor cells to depart from the primary tumor site, invade surrounding tissue, and establish distant metastases. Transforming growth factor β (TGFβ) signaling has been shown to be a major inducer of EMT and to facilitate breast cancer metastasis. However, the role of lncRNAs in this process remains largely unknown. Here we report a genome-wide lncRNA profile in mouse mammary epithelial NMuMG cells upon TGFβ induction of EMT. Among 10,802 lncRNAs profiled, over 600 were up-regulated and down-regulated during the EMT, respectively. Furthermore, we identify that lncRNA-HIT (HOXA transcript induced by TGFβ) mediates TGFβ function, i.e. depletion of lncRNA-HIT inhibits TGFβ-induced migration, invasion, and EMT in NMuMG. LncRNA-HIT is also significantly elevated in the highly metastatic 4T1 cells. Knockdown of lncRNA-HIT in 4T1 results in decrease of cell migration, invasion, tumor growth, and metastasis. E-cadherin was identified as a major target of lncRNA-HIT. Moreover, lncRNA-HIT is conserved in humans and elevated expression associates with more invasive human primary breast carcinoma. Collectively, these data suggest that a subset of lncRNAs such as lncRNA-HIT play a significant role in regulation of EMT and breast cancer invasion and metastasis, and could be potential therapeutic targets in breast cancers.

Fasudil has been proven to be a promising chemotherapeutic drug for various malignancies. However, the potential anticancer effects of fasudil in oesophageal squamous cell carcinoma (ESCC) remain to be established. We confirmed the RhoA activity is inhibited by fasudil in ESCC cells. Then measured the effects of fasudil on apoptosis and autophagy in ESCC. Our study showed fasudil could both induce ESCCs apoptosis and autophagy, and when fasudil-induced autophagy was inhibited by knockdown of the essential autophagy genes (Beclin 1 or ATG7), and pharmacologic agent (chloroquine) treatment, both treatments also significantly sensitized ESCC to fasudil-induced apoptosis, reducing cell viability in vitro. Our study showed autophagy inhibitors combined with fasudil could significantly induce ESCC apoptosis, which may provide a novel therapeutic strategy for ESCC.