不同基坑开挖卸荷方案对既有地铁隧道结构的影响研究

随着城市建设不断推进,地下工程进入快速发展时期,基坑工程对下方既有结构的影响不可忽略。基于此,文章以某换乘地铁站项目上方基坑开挖为例,通过FLAC3D数值模拟软件,分析既有隧道结构上方基坑在一次性开挖、分区开挖、跳挖方案下隧道洞顶结构的变形状态。分析结果表明,无论是否考虑反压作用,3种方案下洞顶结构竖向最大变形排序均为:一次性开挖方案>分区开挖方案>跳挖方案,跳挖方案相较于一次性开挖方案和分区开挖方案隧道洞顶最大位移分别减少了48.6%、38.3%,可有效降低基坑开挖变形量。相关研究可为此类工程施工方案选择提供参考和借鉴。

基于RecurDyn的平架湿地型履带推土机转向性能分析

为使平架湿地型履带推土机在湿地路面实现更高效转向,分析湿地土壤物理特性对该类车辆转向性能的影响.利用PRO/E和RecurDyn软件创建履带推土机三维模型,建立不同含水量湿地路面模型,对模型进行不同载荷下的多体动力学仿真,对比分析履带推土机转向半径、转向极横向偏移量、左侧履带驱动牵引力和右侧履带制动力,得出不同湿地土壤、不同载荷下平架湿地型履带推土机的转向性能参数变化规律.

平架湿地型履带推土机行走系统转向性能仿真研究

基于RecurDyn软件建立平架湿地型履带推土机多体虚拟样机仿真模型及湿地路面模型,以多体动力学理论和方法为基础,对平架湿地型履带推土机在不同湿度路面、不同工况下的转向过程进行动力学仿真和对比分析。通过研究履带推土机在转向时转向角速度、转向半径等参数对转向性能的影响,为湿地型履带推土机行走系统的设计与优化提供一定的参考。

Deficiency of Tfh Cells and Germinal Center in Deceased COVID-19 Patients

Summary:The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease.Understanding the dysregulated human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic.In this study,we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia(FOP)patients who underwent lung surgery and served as controls.We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients.In contrast to the FOP patients,Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients.This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients.In summary,our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity.Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.

Notch1 Drives the Formation and Proliferation of Intrahepatic Cholangiocarcinoma

The molecular mechanisms underlying the development of intrahepatic cholangiocarcinoma(ICC)are not clear yet.In this study,we investigated the involvement of Notch1 in the development of ICC.The cDNA microarray analysis showed that Notch1 expression was higher in ICC tissues than in normal biliary epithelial cells.Stable transfection of Notchl receptor intracellular domain(NICD1)by hydrodynamic tail vein injection induced ICC formation in mice.Western blotting confirmed that Notchl signaling was activated in human ICC cell lines and mouse ICC tissues.Silencing Notchl with specific short interfering RNA(siRNA)inhibited the proliferation of ICC cells.Flow cytometry and Western blotting indicated that apoptosis was induced in Notchl-silenced ICC cells compared with controls.Additionally,Notchl silencing was associated with the inhibition of hairy and enhancer of split-1(Hes1)and activation of the phosphatase and tensin homolog(PTEN)/p53 pathway.Taken together,these data suggest that Notchl drives ICC formation and proliferation;downregulation of Notchl induces apoptosis in ICC cells;Notchl signaling may serve as a novel therapeutic target for the treatment of ICC.

Prostate-specific membrane antigen expression in hepatocellular carcinoma,cholangiocarcinoma,and liver cirrhosis

BACKGROUND Primary liver cancer includes three subtypes:Hepatocellular carcinoma(HCC),intrahepatic cholangiocarcinoma(CCA),and combined hepatocellular carcinoma.Patients with primary liver cancer experienced poor prognosis and high mortality,so early detection of liver cancer and improved management of metastases are both key strategies to reduce the death toll from liver cancer.Prostate-specific membrane antigen(PSMA)expression in the tumor-associated neovasculature of nonprostate malignancies including liver cancer has been reported recently,but conclusive evidence of PSMA expression based on the pathological type of liver cancer remains limited.AIM To study the expression of PSMA in HCC,CCA,and liver cirrhosis.METHODS A total of 446 formalin-fixed paraffin-embedded(FFPE)liver tumor and liver cirrhosis tissue samples were obtained retrospectively from the Pathology Department of Tongji Hospital.Immunohistochemistry was used to detect PSMA expression in these 446 FFPE liver biopsy specimens(213 HCC,203 CCA,and 30 liver cirrhosis).The tumor compartment and the associated neovascular endothelium were separately analyzed.PSMA expression was examined by two certified pathologists,and the final results were presented in a 4-point scoring system(0-3 points).Correlation between PSMA expression and clinicopathological information was also assessed.RESULTS PSMA was expressed primarily in the neovascular endothelium associated with tumors.The positive rate of PSMA staining in HCC was significantly higher than that in CCA(86.8%vs 79.3%;P=0.001)but was only 6.6%in liver cirrhosis(P=0.000).HCC cases had more 3-score PSMA staining than CCA had(89/213,41.8%vs 35/203,17.2%;P=0.001).PSMA expression correlated positively with the stage and grade of HCC and CCA.In both liver cancer subtypes,there were more PSMA+cases in stages III–V diseases than in stages I and II.High staining intensity of PSMA was more frequently observed in liver cancers at high grade and advanced stage.There was no significant association of PSMA expression with sex,age,region,α-fetoprotein,hepatitis B surface antigen,or tumor size in both tumor subtypes.CONCLUSION Neovascular PSMA may be a promising marker to differentiate HCC from liver cirrhosis and a prognostic marker for anti-tumor angiogenesis therapy for HCC.

Immunohistochemical panel of glypican-3, hepatocyte paraffin antigen-1, arginase-1, cytokeratin-19, and human epithelial membrane antigen for the differential diagnosis of liver tumors

Objective Clinical immunohistochemistry plays an increasingly important role in pathologic diagnosis. We investigated the usefulness of an immunohistochemical panel of glypican-3 (GPC3), hepatocyte paraffin antigen-1 (HepPar-1), arginase-1 (Arg-1), cytokeratin-19 (CK19), and human epithelial membrane antigen (EMA) for the differential diagnosis of liver tumors. Methods Two hundred and thirty-five immunohistochemical sections of hepatocellular carcinoma (HCC;120 cases), intrahepatic cholangiocarcinoma (ICC;50 cases), combined hepatocellular and cholangiocarcinoma (CHC;17 cases), metastatic adenocarcinoma (20 cases), and benign liver lesions (28 cases) were obtained from the Department of Pathology at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. The sensitivity and specificity of the combined biomarkers GPC3/HepPar-1/Arg-1/CK19/EMA for the differential diagnosis of HCC, ICC, and CHC were calculated and analyzed retrospectively. Results The combined biomarkers GPC3+/CK19– had the highest specificity (98.3%) for diagnosing HCC, with a sensitivity of 60.0%. The specificity of GPC3–/HepPar-1–/Arg-1–/CK19+/EMA+ for diagnosing ICC was 93.0%, with a sensitivity of 76.0%. The specificity of GPC3+/HepPar-1+/Arg-1+/CK19+/EMA+ for diagnosing CHC was 95.9%, with a sensitivity of 52.9%. Conclusion The combined biomarkers GPC3/HepPar-1/Arg-1/CK19/EMA greatly improved the specificity of liver tumor diagnosis. We believe that clinical pathological work could improve the original determination of liver nodules.

Proteomic Stratification of Prognosis and Treatment Options for Small Cell Lung Cancer

Small cell lung cancer(SCLC)is a highly malignant and heterogeneous cancer with limited therapeutic options and prognosis prediction models.Here,we analyzed formalin-fixed,paraffin-embedded(FFPE)samples of surgical resections by proteomic profiling,and stratified SCLC into three proteomic subtypes(S-I,S-II,and S-III)with distinct clinical outcomes and chemotherapy responses.The proteomic subtyping was an independent prognostic factor and performed better than current tumor–node–metastasis or Veterans Administration Lung Study Group staging methods.The subtyping results could be further validated using FFPE biopsy samples from an independent cohort,extending the analysis to both surgical and biopsy samples.The signatures of the S-II subtype in particular suggested potential benefits from immunotherapy.Differentially overexpressed proteins in S-III,the worst prognostic subtype,allowed us to nominate potential therapeutic targets,indicating that patient selection may bring new hope for previously failed clinical trials.Finally,analysis of an independent cohort of SCLC patients who had received immunotherapy validated the prediction that the S-II patients had better progression-free survival and overall survival after first-line immunotherapy.Collectively,our study provides the rationale for future clinical investigations to validate the current findings for more accurate prognosis prediction and precise treatments.

Hilar cholangiocarcinoma: Pathology and tumor biology

Hilar cholangiocarcinoma,first described by Klatskin in 1965,is a relatively rare tumor arising from the bile ducts.The histomorphological features of hilar cholangiocarcinoma are identical with other extra-and intra-hepatic bile duct carcinomas.The most common disease associated with cholangiocarcinoma is primary sclerosing cholangitis.The development of cholangiocar-cinoma is a multistep process associated with several mutations in oncogenes and tumor-suppressor genes.Based on macroscopic appearance,three distinct subtypes have been described:sclerosing,nodular,and papillary.Microscopically,more than 95%of tumors are adenocar-cinomas.Hilar cholangiocarcinoma is a slowly growing tumor and tends to spread longitudinally along the bile ducts with neural,perineural,and subepithelial extension.Lymph node invasion can be found in 30%–50%patients at the time of diagnosis,but blood-born metastases are rare and usually occur at late stages.

Design,synthesis and evaluation of PPAR gamma binding activity of 2-thioxo-4-thiazolidinone derivatives

We designed and synthesized a series of 2-thioxo-4-thiazolidinone derivatives and evaluated them on peroxisome proliferator activated receptor γ（PPARγ） binding activities.Through the biological assays,compounds 18 and 38 were highlighted with K_i values of 12.15 nmol/Land 14.46 nmol/L,respectively.Then structure-activity relationship（SAR） was analyzed to screen privileged structural modifications.Moreover,molecular fitting of these compounds onto the approved drug Rosightazone in the PPARγligand binding domain was performed to elucidate the SAR and explore potential receptor-ligand interactions.These results demonstrate that the 2-thioxo-4-thiazolidinones can be considered as new promising molecular probes with excellent binding activities to PPARγ.

Expert Consensus on Pathological Diagnosis of Intrahepatic Cholangiocarcinoma(2022 version)

Intrahepatic cholangiocarcinoma(iCCA)can originate from the large bile duct group(segment bile ducts and area bile ducts),small bile duct group(septal bile ducts and interlobular bile ducts),and terminal bile duct group(bile ductules and canals of Hering)of the intrahepatic biliary tree,which can be histopathological corresponding to large duct type iCCA,small duct type iCCA and iCCA with ductal plate malformation pattern,and cholangiolocarcinoma,respectively.The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies,tissue structures,growth patterns,invasive behaviors,immunophenotypes,molecular mutations,and surgical prognoses.For these reasons,this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA,mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.