Exploring the impact of non-small cell lung cancer tumor microbiome on the efficacy of chemotherapy and immune checkpoint inhibitors

Background:This study aimed to investigate the potential of intratumoral microbiota,gut microbiome,peripheral blood T-cell subsets,and inflammatory markers as predictive biomarkers for antitumor efficacy in patients with non-small cell lung cancer.Methods:This study observed patients with metastatic non-driver mutation non-small cell lung cancer who were initially diagnosed at the First Affiliated Hospital of Dalian Medical University’s Department of Oncology from August 2021 to July 2022 and completed at least four cycles of chemotherapy combined with immune checkpoint inhibitor treatment.Lung biopsy tissues,fecal,and peripheral blood samples were collected from these patients.Based on the efficacy of the combined chemotherapy and immunotherapy,patients were divided into an effective group and an ineffective group.The tumor microbiota,gut microbiome,peripheral blood T-cell subsets,and inflammatory markers were compared between the two groups.The lung and fecal microbiota were analyzed using 16S rRNA high-throughput sequencing.Flow cytometry was used to detect T-cell subsets,and enzyme-linked immunosorbent assay was employed to measure inflammatory factors.Results:A total of 21 patients were observed.There were significant differences in the tumor microbiota between the responsive and non-responsive groups,particularly the proportion of the genera Sphingomonas and Pseudomonas.The gut microbiome composition changed after treatment,but there were no differences between the two groups before treatment.There were no significant differences in T-cell subsets and inflammatory markers between the responsive and non-responsive groups.Conclusion:The composition of intratumoral microbiota in non-small cell lung cancer patients may serve as an indicator of response to chemotherapy combined with immunotherapy.The predictive value of gut microbiota,T-cell subsets,and inflammatory markers appears limited.Future research should further validate the predictive role of changes in gut microbiota on treatment outcomes.

机械密封技术在煤油泵方面的应用现状与分析（英文）

煤油泵是航天设备中的重要部件,而机械密封技术又是保证煤油泵正常可靠工作的关键技术,综述了机械密封技术在以煤油泵为代表的低粘度介质液压泵领域的发展状况。首先,介绍了机械密封技术的基本原理;随后,分别从国外和国内两个角度论述了煤油泵中采用的机械密封方法和主要产品;然后,针对煤油泵的特殊工况总结了相对应的机械密封的关键技术;最后,对机械密封技术在煤油泵领域的应用进行了分析和总结。

DNA ploidy analysis and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma

AIM: To investigate DNA ploidy and expression of MMP-9,TIMP-2, and E-cadherin in gastric carcinoma and to explore the mechanism of invasion and metastasis of gastric carcinoma.METHODS: Immunohistochemical methods were used to detect the expressions of MMP-9, TIMP-2, and E-cadherin in 156 cases, including 99 cases of gastric carcinoma, 16cases of adjacent noncancerous mucosa, 16 cases of distant metastases and 25 cases of metastatic lymph node (LN) from gastric carcinoma. Flow cytometry DNA ploidy and S-phase fraction (SPF) analysis were performed on 57 cases, including 47 cases of gastric cancer, 6 cases of adjacent noncancerous mucosa, and 4 cases of distant metastatic cancer.RESULTS: The expression of MMP-9 was significantly correlated with Lauren's classification, Borrmann's classification, LN metastasis, tumor metastasis, and TNM stage, as well as depth of invasion (all P＜0.05). The positive rate was lower in noncarcinoma than in carcinoma (31.3% vs 66.7%, P＜0.01). The expression of TIMP-2was significantly correlated with Borrmann's classification,LN metastasis, and the depth of invasion (all P＜0.05).The expression of E-cadherin was significantly correlated with differentiation, Lauren's classification, Borrmann's classification, and LN metastasis, as well as the depth of invasion (P＜0.01 or ,P＜0.05). E-cadherin was less expressed in carcinoma than in noncarcinoma (42.4% vs 87.5%,P＜0.01). There was a positive correlation between MMP-9and TIMP-2 and a negative correlation between MMP-9and E-cadherin, but no correlation between TIMP-2 and E-cadherin. Also there was a positive correlation between DNA aneuploid rate and differentiation and LN metastasis.SPF that was higher than 15% was positively correlated with tumor size, differentiation and LN metastasis. And there was a significant difference between carcinoma and noncarcinoma in DNA aneuploid rate and SPF.CONCLUSION: With tumor progression and development of heterogeneity, the abnormal expressions of MMP-9,TIMP-2, and E-cadherin or DNA aneuploid rate or high SPF gradually increases, suggesting that they play a crucial role in gastric carcinoma progression.

Relationship between expressions of E-cadherin and alpha-catenin and biological behaviors of human pancreatic cancer

OBJECTIVES: To investigate the expressions of E-eadherin and alpha-catenin in pancreatic carcinoma and their relationship with biological behaviors, and clarify the mechanism of invasion and metastasis of pancreatic cancer. METHODS: The expressions of E-eadherin and alpha-catenin was examined in 47 patients with infiltrative ductal adenocarcinoma of the pancreas and 12 specimens of normal pancreatic tissues by immunohistochemical technique (PicTure^(TM) two-step method). Proliferation cell nuclear antigen (PCNA) was tested as an index of the proliferation degree of pancreatic cancer cells. RESULTS: The immunoreactivity of E-cadherin and alpha-catenin was expressed by normal ductal and acinar cells with strong membranous staining at the intercellular border in 12 specimens of normal pancreatic tissues. The abnormal rate of E-cadherin expression in pancreatic cancer was 53.2% (25/47), and it was significantly related to differentiation, high proliferation degree and lymph node and liver metastases (P<0.O1, 0.05, 0.05 and O.01, respectively). 61.7% patients with pancreatic cancer (29/47) showed abnormal expression of alpha-catenin. There was a good correlation among alpha-catenin expression, histological grade, and lymph node and liver metastases (P<0.05, 0.05 and 0.01, respectively). No significant association was found among abnormal expressions of E-cadherin and alpha-catenin, tumor size, invasion, and 1-year survival rate of patients ( P>0.05, all). There was a positive relationship between the expressions of E-cadherin and alpha-catenin in the 47 patients with pancreatic cancer (P<O.O1, r=0.88). CONCLUSIONS: Pancreatic cancer likely occurs in case of the inactivation of E-cadherin and alpha-catenin genes and abnormal expression of proteins, which significantly correlate with tumorigenesis, proliferation, differentiation, and lymph node or liver metastasis of pancreatic cancer.

Design and evaluation of a Laval-type supersonic atomizer for low-pressure gas atomization of molten metals

A Laval-type supersonic gas atomizer was designed for low-pressure gas atomization of molten metals. The principal design ob-jectives were to produce small-particle uniform powders at lower operating pressures by improving the gas inlet and outlet structures and op-timizing structural parameters. A computational fluid flow model was developed to study the flow field characteristics of the designed atom-izer. Simulation results show that the maximum gas velocity in the atomization zone can reach 440 m＆#183;s-1;this value is independent of the atomization gas pressure P0 when P0〉0.7 MPa. When P0=1.1 MPa, the aspiration pressure at the tip of the delivery tube reaches a mini-mum, indicating that the atomizer can attain the best atomization efficiency at a relatively low atomization pressure. In addition, atomization experiments with pure tin at P0=1.0 MPa and with 7055Al alloy at P0=0.8 and 0.4 MPa were conducted to evaluate the atomization capa-bility of the designed atomizer. Nearly spherical powders were obtained with the mass median diameters of 28.6, 43.4, and 63.5μm, respec-tively. Compared with commonly used atomizers, the designed Laval-type atomizer has a better low-pressure gas atomization capability.

Design and Atomization Characteristic of Laval-style Annular Slot Nozzle

Gas mass flux rate,metal mass flux rate and outlet gas velocity are three atomization scale parameters which greatly affect the atomization efficiency. A Laval-style annual slot supersonic nozzle is designed by optimizing the geometric parameters of delivery tube outlet and gas outlet to obtain applicable atomization scale parameters. A computational fluid flow model is adopted to investigate the effect of atomization gas pressure ( P0 ) on the gas flow field in gas atomization progress. The numerical results show that the outlet gas velocity of the nozzle is not affected by P0 and the maximum gas velocity reaches 452 m / s. The alternation of aspiration pressure ( ΔP) is caused by the variations of stagnation pressure and location of Mach shock disk, and hardly by the location of stagnation point. The aspiration pressure is found to decrease as P0 increases when P0 < 1. 3 MPa. However,at a higher atomization gas pressure increasing P0 causes an opposite: the aspiration pressure atomization increases with the gas pressure,and keeps a plateau when P0 > 2. 0 MPa. The minimum aspiration pressure ΔP = - 70 kPa is obtained at P0 = 1. 3 MPa. The results indicate that the designed Laval- style annual slot nozzle has well atomization characteristic at lower atomization pressure.

Thermo-elasto-visco-plastic finite element analysis on formation and propagation of off-corner subsurface cracks in bloom continuous casting

The formation and propagation of the popular off-corner subsurface cracks in bloom continuous casting were investigated through thermo-mechanical analysis using three coupled thermo-mechanical models. A two-dimensional thermo-elasto-visco-plastic finite element model was developed to predict the mould gap evolution, temperature profiles and deformation behavior of the solidified shell in the mould region. Then, a three-dimensional model was adopted to calculate the shell growth, tempera- ture history and the development of stresses and strains of the shell in the following secondary cooling zones. Finally, another three-dimensional model was used to analyze the stress distributions in the straightening region, The results showed that the off-corner cracks in the shell originated from the mould owing to the tensile strain developed in the crack sensitive regions of the solidification front, and they could be driven deeper by the possible severe surface temperature rebound and the extensive tensile stress in the secondary cooling zone, especially upon the straightening operation of the bloom casting. It is revealed that more homogenous shell temperature and thickness can be obtained through optimization of mould corner radius, casting speed and secondary cooling scheme, which help to decrease stress and strain concentration and therefore prevent the initiation of the cracks.