Adaptor Proteins, Signal Transducing ; chemistry ; metabolism ; Animals ; Apoptosis ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Neoplasms ; pathology ; Phosphorylation ; Protein Isoforms ; RNA-Binding Proteins ; chemistry ; metabolism ; Transcription Factors ; antagonists & inhibitors

Environmental Health ; Occupational Health ; Social Responsibility

Humans ; Occupational Diseases ; prevention & control ; Social Responsibility

Environmental Pollution ; prevention & control ; Metals, Heavy

Humans ; Occupational Health Services ; Transients and Migrants

Humans ; Lung ; pathology ; Physical Examination ; Pneumoconiosis ; diagnosis ; Thoracotomy

Objective To synthesize 18F-FMISO and analyze the quality of the product.Methods 1-(2'-nitro-l'-imidazolyl)-2-O-tetrahydropyranyl-O-trluendulfonylpropanediol (NITIT) was taken as the precursor and simple one pot method was used.CFN-MPS-100 fluorine multifunction radiopharmaceutical chemical synthesis module was adopted to complete the radioactive fluorination reaction in a closed flat flask,and the crude product was purified by semi-preparative HPLC,the solvent was removed by rotary evaporation.Then 15 ml saline was added into the product to get 18F-FMISO injection.Radio-HPLC and radio-TLC were applied for quality control.Results 18F-FMISO was obtained in 60 min with the radiochemical yield of (32±5.0)％ (no decay corrected,n=25).The radiochemical purity was above 99.0％ and still above 98.5％ after 6 h.The radioactive concentration was above 1.11 × 1012 Bq/L.The product was colorless solution,with pH value of 7.0.The radioactive nuclear purity was more than 99％.The K222 was less than 25 μg/ml.Conclusion 18 F-FMISO could be synthesized with automatic synthesis method based on the CFN-MPS-100 fluorine multifunction module.The labeling rate,stability and chemical purity are high.

Objective To confirm whether taxotere combined with mild hyperthermia will have synergistic effects,and to explore their joint mechanism of action.Methods Firstly the effective concentration of taxotere was determined by using MTT method to observe the effect of docetaxel on proliferation of human breast cancer cell line MCF-7.Then three samples of in vitro cultured human breast carcinoma MCF-7 cells were prepared,termed the the taxotere group,the taxotere plus mild hyperthermia group and the control group,and treated with effective concentration of taxotere exclusively or in combination with mild hyperthermia,or left without any special treatment.The taxotere plus mild hyperthermia group was subdivided into 5 subgroups according to the temperatures used (39.0 ℃,39.5 ℃,40.0 ℃,40.5 ℃,41.0 ℃) MTT assays were used to measure the proliferation and invasive capacity of the cells and their effective concentrations.Flow cytometry was used to detect cell apoptosis rates and any cell cycle changes in the control group.Western blotting was used to detect any changes in the expression of mitogen-activated protein kinases (MAPKs),Bcl-2/Bax,heat shock protein-70 (HSP-70) and P-gp.Results The taxotere with mild hyperthermia group demonstrated a significantly higher rate of apoptosis than that in the taxotere and control groups.There were also more cells in the G2/M phase observed.Combining taxotere with mild hyperthermia was found after 24 h to have significantly increased p-ERK,p-JNK,p38,HSP-70 and P-gp protein levels and to have significantly decreased Bcl-2 protein expression in contrast with the other two groups.Conclusions Combining taxotere with mild hyperthermia showed synergistic effects in vitro.It seemed to be limiting the accumulation of MCF-7 cells in the G2/M phase and activating the signal pathways of MAPKs while inhibiting the activation of Bcl-2/Bax signal pathways.Combining taxotere and mild hyperthermia can accelerate the expression of HSP70 and P-gp in MCF-7 cells.Hyperthermia might induce chemotherapy resistance.

Objective To explore the association between ratio index of gamma glutamyl transpeptidase/platelet (GPRI) and the prognosis of patients with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) before liver resection. Methods A total of 368 patients underwent liver resection for HBV-related HCC were retrospectively analyzed in this study. Patients were divided into high GPRI group (n=184, GPRI≥0.38) and low GPRI group (n=184, GPRI<0.38). Clinicopathologic characteristics including overall survival (OS) and disease-free survival (DFS) were compared between the two groups. Independent risk factors influencing DFS and OS were determined by Cox multivariate analysis. Results Compared to low GPRI group, there were higher levels of serum total bilirubin and alanine aminotransferase, higher proportions of tumor diameter larger than 10 cm, amount of tumou more than 3, and patients with macrovascular invasion and intermediate or advanced HCC in high GPRI group (all P<0.05). Values of DFS at 1, 3, and 5 years were significantly lower in high GPRI group (50.8%, 16.9%and 5.7%) than those in low GPRI group (69.0%, 33.3%, 10.7%;P=0.001). Values of OS at 1, 3, and 5 years were also significantly lower in high GPRI group (75.0%, 51.8%and 36.0%) than those in low GPRI group (89.8%, 72.8%and 63.2%;P<0.05). Cox multivariate analysis also demonstrated that GPRI ≥0.38 was an independent risk factor for DFS and OS in patients with HBV-related HCC after liver resection. Conclusion Preoperative GPRI can predict tumor recurrence and long-term survival in patients with HBV-related HCC after liver resection.

This study aimed to investigate the mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" (GX) on phlegm and blood stasis syndrome (PBSS) rats combining the methods of network pharmacology and experimental verification. Animal experiment ethical requirements were approved by the Ethical Committee Experimental Animal Center of Anhui University of Chinese Medicine (grant number: AHUCM-rats-2021070). Based on the HPLC-Q-TOF-MS analysis and database, 69 chemical constituents of GX and 163 targets of GX for the treatment of phlegm and blood stasis-related cardiovascular diseases were obtained. Then, key targets such as serine/threonine kinase 1 (Akt1), tumor necrosis factor (TNF), interleukin 6 (IL6), vascular endothelial growth factor A (VEGFA), cellular tumor antigen p53 (Tp53) were screened. Pathway analysis showed that the targets of GX in the treatment of phlegm and blood stasis-relate cardiovascular diseases were mainly involved in PI3K/Akt signaling pathway, sphingolipid metabolism, platelet activation, hypoxia inducible factor-1 (HIF-1), ras-proximate-1 (rap1) and other signaling pathways. In addition, molecular docking analysis showed that apigenin, cucurbitacin D, linolenic acid and kaempferol and other key components had potential binding ability with Akt1, TNF, IL6, VEGFA and Tp53. In the animal experiments, compared to the phlegm and blood stasis syndrome group, GX could significantly improve the traditional Chinese medicine syndrome score, blood lipid, vascular endothelial structure disorders and reduce serum endothelin-1 (ET-1) level, increase serum nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) levels, which could restore aortic endothelial function. In addition, the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in aorta could be significantly reduced, which could improve the vascular endothelial injury of aorta. Western blot revealed that GX could significantly decrease the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and Akt in aorta. This study revealed the mechanism of GX in treatment of phlegm and blood stasis-relate cardiovascular diseases is consistent with the characteristics of multiple ingredients, multiple targets and multiple pathways. In addition, this study also clarified that the reversal of pathological of phlegm and blood stasis syndrome rats may be related to GX inhibiting PI3K/Akt signaling pathway, which could improve vascular inflammation and vascular endothelial function injury.