Objective To observe the effects of the intervention of Didang Decoction at different times on changes of AMPK signaling pathway related factors in macrovascular endotheliocytes of diabetic rats; To discuss the mechanism of mitochondria energy metabolism regulating the AMPK signaling pathway for macrovascular endothelial defense function. Methods Injection of STZ into the caudal vein and administration of high fat diet wer used to generate diabetic rat model. All rats were randomly divided into the following 7 groups: control, model, metformin, simvastatin, early-, middle-, and late-stage Didang Decoction group. Western blot was used to detect the expressions of APMKα1 and PGC-1α in rat aortic endothelial cells. Changes in the intracellular AMP and ATP levels were detected by ELISA. Real time fluorescence quantitative PCR was used to detected mRNA expressions of Caspase-3, eNOS, and Bcl-2 in tissue of thoracic aorta. Results Compared with the model group, the expressions of AMPKα1 and PGC-1α in the early-stage and middle-stage Didang Decoction group and simvastatin group increased (P<0.05); the gene expressions of Bcl-2, and eNOS significantly increased in the early-stage Didang Decoction group and simvastatin group (P<0.05), while the expressions of Caspase-3 decreased significantly (P<0.05). The expression of ATP increased significantly and the expression of AMP decreased significantly in the early-stage Didang Decoction group and simvastatin group (P<0.05), and the best effects were shown in the early-stage Didang Decoction group. Conclusion Early intervention of Didang Decoction can enhance energy metabolism in the mitochondria of macrovascular endothelial cells by regulating the AMPK signaling pathway, and then plays a role in strengthening the defense function of macrovascular endothelial cells.

Objective:To investigate the clinicopathological characteristics of breast squamous cell carcinoma and to analyze the relationship between its immune microenvironment tumor infiltrating lymphocytes (TILs) and prognosis.Methods:Forty-four cases of primary squamous cell carcinoma of the breast diagnosed and treated in the First Affiliated Hospital of Air Force Medical University, Xi′an, China from January 2006 to July 2022 were selected. Their clinicopathological characteristics were analyzed. The cell composition of TILs was evaluated using immunohistochemistry (Mainly markers of B lymphocytes, T lymphocytes and plasma cells). The relationship between TILs and prognosis was also analyzed.Results:The 44 patients of breast squamous cell carcinoma were all female and all were invasive carcinoma. Eight cases (8/44, 18.2%) were squamous cell carcinoma, while 36 cases (36/44, 81.8%) were mixed squamous cell carcinoma. The mixed components included non-specific carcinoma and spindle cell metaplastic carcinoma (17 cases each). One case contained ductal carcinoma in situ of the breast and 1 case contained tubular carcinoma. The proportion of squamous cell carcinoma was 10% to 90%. The cases with pure squamous cell carcinoma often had a large cystic cavity, which was lined by atypical squamous epithelium, while infiltrating squamous cell carcinoma nests were seen in the breast tissue around the cystic cavity. Immunohistochemical staining showed that p63 and CK5/6 were expressed in the squamous cell carcinoma component, but ER, PR and HER2 were not, except for one case of HER2 1+. The positive rates of TRPS1 and PDL-1 were 76% and less than 1%, respectively. Fifteen cases were in the high TILs group (TILs≥30%) and 29 cases were in the low TILs group (TILs<30%). Twenty-three patients were followed up for 5 to 118 months. Among them, 12 died within 3 years and 9 were alive at the end of the follow up. There was no significant difference in TNM stage, TILs and prognosis between simple squamous cell carcinoma and mixed squamous cell carcinoma.Conclusions:Breast squamous cell carcinoma can be divided into simple squamous cell carcinoma and mixed squamous cell carcinoma. There are differences in gross findings and histology between the simple and mixed squamous cell carcinoma of the breast. Sufficient samples should be taken to avoid missing the diagnosis of a minor squamous component. The prognosis of patients with high TILs is significantly better than that of patients with low TILs. The expression rate of TRPS1 in primary squamous cell carcinoma of breast is high and helpful to the differential diagnosis from metastatic squamous cell carcinoma.

Objective:To perform harmonization based on the ComBat method for PET brain imaging scanned by different types of scanners from the same manufacturer and explored its effect on center effect.Methods:The three-dimensional (3D) Hoffman brain model was scanned by two different PET/CT instruments (Siemens Biograph64 TruePoint and Biograph128 mCT). Fourteen healthy subjects (8 males, 6 females, age: (57.7±9.5) years) underwent 18F-FDG PET/CT on Siemens Biograph64 TruePoint and 12 healthy subjects (9 males, 3 females, age: (55.8±10.5) years) underwent 18F-FDG PET/CT on Siemens Biograph128 mCT (all from Huashan Hospital, Fudan University; from November 2020 to March 2023). The whole brain was divided into 116 brain regions based on the anatomical automatic labeling (AAL) brain template. The ComBat method was applied to harmonized the PET data from brain model and healthy subjects. Mann-Whitney U test was performed on the radioactive counts and SUV ratios (SUVR) before and after homogenization acquired by both PET/CT instruments. Voxel-based statistical parametric mapping (SPM) independent-sample t test was also performed on data of healthy subjects. Results:In 3D Hoffman brain model, radioactivity counts (5 590.33(4 961.67, 6 102.95) vs 6 116.03(5 420.97, 6 660.66); z=-9.35, P<0.001) and SUVR (1.35(1.19, 1.47) vs 1.37(1.21, 1.49); z=-3.63, P<0.001) were significantly different between the two PET/CT scanners before harmonization and not after harmonization (radioactivity counts: 5 845.95(5 192.68, 6 378.63) vs 5 859.17(5 193.84, 6 380.52); SUVR: 1.35(1.20, 1.48) vs 1.36(1.20, 1.49); both z=-0.68, both P=0.498). In the healthy subjects, radioactive counts in 19 brain regions (12 422.78(11 181.60, 13 424.28)-18 166.40(15 882.80, 18 666.27); z values: from -3.24 to -2.06, all P<0.05) and SUVR in 40 brain regions (1.46(1.41, 1.52)-2.28(2.16, 2.36); z values: from -3.65 to -1.70, all P<0.05) were significantly different between the two scanners before harmonization, while after homogenization there were no statistical differences for all 116 brain regions (radioactivity counts: 9 243.55(8 502.38, 9 854.87)-20 419.60(19 931.51, 21 179.43); z values: from -0.72 to 0, all P>0.05; SUVR: 1.04(1.01, 1.09)-2.32(2.24, 2.40); z values: from -0.82 to 0, all P>0.05). SPM showed that significant differences of glucose metabolism in the cerebral cortex, basal ganglia, midbrain and cerebellum were found in healthy subjects between the two PET/CT scanners before homogenization, and brain regions with obvious differences reduced after homogenization. Conclusion:ComBat harmonization method is efficient at removing the center effect among different types of PET/CT scanners from the same manufacturer and may provide a simple and easy-to-implement homogenization for multicenter brain imaging studies.