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OBJECTIVE To establish the drug-induced liver injury （DILI） surveillance and assessment system （DILI-SAS）， and to improve the diagnostic efficiency of clinical DILI. METHODS The DILI-SAS was constructed by using natural language processing technology to mine and utilize all inpatient medical record data， and combined with Roussel Uclaf causality assessment method （RUCAM）. The medical records of 19 445 hospitalized patients from August 2022 to January 2023 were detected to verify the performance of the system and manually analyze the basic data of patients with DILI and the distribution of the first suspected drugs. RESULTS The overall accuracy rate of the DILI-SAS system was 91.95%， and the recall rate was 93.20%. Seventy-five DILI cases were detected， and the DILI incidence rate was 385.70/100 000 people. The efficiency of DILI monitoring by human- computer coupling was increased by about 60 times of manual monitoring； males （61.33%） and patients over 60 years old （56.00%） were the most common in the 75 cases of DILI. The clinical type of liver injury was hepatocyte injury （69.33%）， the incubation period was mainly 5-90 days after treatment （62.67%）， and the RUCAM score between 3 and 5 was the most common （66.67%）； pharmacological distribution of the first suspected drugs was mainly dihydropyridines， HMG CoA reductase inhibitors， proton pump inhibitors， etc. The specific drugs were atorvastatin， omeprazole， ceftriaxone， metronidazole and other drugs. CONCLUSIONS The establishment of DILI-SAS can improve the evaluation efficiency on the basis of ensuring the accuracy degree， and provide a solution for the early identification， diagnosis and evaluation of clinical DILI.
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Genome packaging is a fundamental process in a viral life cycle and a prime target of antiviral drugs. Herpesviruses use an ATP-driven packaging motor/terminase complex to translocate and cleave concatemeric dsDNA into procapsids but its molecular architecture and mechanism are unknown. We report atomic structures of a herpesvirus hexameric terminase complex in both the apo and ADP•BeF3-bound states. Each subunit of the hexameric ring comprises three components-the ATPase/terminase pUL15 and two regulator/fixer proteins, pUL28 and pUL33-unlike bacteriophage terminases. Distal to the nuclease domains, six ATPase domains form a central channel with conserved basic-patches conducive to DNA binding and trans-acting arginine fingers are essential to ATP hydrolysis and sequential DNA translocation. Rearrangement of the nuclease domains mediated by regulatory domains converts DNA translocation mode to cleavage mode. Our structures favor a sequential revolution model for DNA translocation and suggest mechanisms for concerted domain rearrangements leading to DNA cleavage.
ABSTRACT
Genome packaging is a fundamental process in a viral life cycle and a prime target of antiviral drugs. Herpesviruses use an ATP-driven packaging motor/terminase complex to translocate and cleave concatemeric dsDNA into procapsids but its molecular architecture and mechanism are unknown. We report atomic structures of a herpesvirus hexameric terminase complex in both the apo and ADP•BeF3-bound states. Each subunit of the hexameric ring comprises three components-the ATPase/terminase pUL15 and two regulator/fixer proteins, pUL28 and pUL33-unlike bacteriophage terminases. Distal to the nuclease domains, six ATPase domains form a central channel with conserved basic-patches conducive to DNA binding and trans-acting arginine fingers are essential to ATP hydrolysis and sequential DNA translocation. Rearrangement of the nuclease domains mediated by regulatory domains converts DNA translocation mode to cleavage mode. Our structures favor a sequential revolution model for DNA translocation and suggest mechanisms for concerted domain rearrangements leading to DNA cleavage.
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Most organisms contain glutamate dehydrogenase (E.C. 1.4.1.2-1.4.1.4). In eukaryotes, the enzyme is mainly present in mitochondria. This enzyme plays a vital role in the metabolism of nitrogen and carbon and the signaling pathway. Studies have found that glutamate dehydrogenase has a certain relationship with the occurrence and development of tumors, which is significant for tumor research, but reviews on its relationship with human tumors are rare. This review summarized the relationship between glutamate dehydrogenase and breast cancer, glioma, colorectal cancer and ovarian cancer, etc, thus providing assistance for related research.
Subject(s)
Humans , Carbon , Glioma , Glutamate Dehydrogenase , Mitochondria , NitrogenABSTRACT
Objectives:To study the relationship between angiogenesis,proliferation and lymph node metastasis in rectal cancer. Methods: Forty six rectal cancer specimens were examined immunohistochemically. The intratumor microvessel density(MVD), vascular endothelial growth factor (VEGF)expression positive rate and Ki 67 label index(Ki 67 LI) were detected and their relationship with tumor invasion and lymph node metastasis were analyzed. Results: The MVD, VEGF expression positive rate and Ki 67 LI increased significantly( P
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Objectives：To investigate the pathological and clinical effect of preoperative arterial infusion chemotherapy on breast cancers.Methods:Twenty patients with breast carcinoma received regional arterial angiography by Seldinger's procedure followed by arterial infusion chemotherapy.Sixteen patients who didn't undergo preoperative chemotherapy were selected as controls.All the operation specimens were analyzed by the same pathologist.Results:Histological analysis of the two groups revealed the following results:① cancer tissue necrosis increased in the arterial chemotherapy group;②karyopyknosis,karyorrhexis coagulation and necrosis of cytoplasm around the vascular vessels as well as interstitial edema were found in the tumor tissue,invasion of inflammatory cells,intimal proliferation thrombus and inflammation of vessels could also be seen.All the changes were much severe in the infusion chemotherapy group than in the controlled group;Conclusions:Histological changes are significant after preoperative arterial infusion chemotherapy for breast carcinoma.
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Objective To explore the effect of preoperative radiotherapy on angiogenesis of rectal cancer. Methods Twenty patients with advanced lower rectal carcinoma received preoperative radiation with a dosage of 30～40 Gy each time for a total of 15～20 sessions during a period of 3～4 weeks. The definitive surgery was performed 7～10 days after radiotherapy. Another 20 patients undergoing tumor resection without preoperative radiotherapy served as control. Tumor sample was sent for pathology. The expression of vascular endothelial growth factor (VEGF) and CD34 in the rectal cancer were detected immunohistochemically. The intratumoral microvessel density (MVD) was measured. Results Fifteen patients were found with grade Ⅱ and five patients with grade Ⅲ tissue response in radiotherapy group. The diameter of intratumoral microvessel was smaller in radiotherapy group than in control group( P