Objective To analyze the characteristics of real-world adverse drug events(ADEs)of trabectedin based on the FDA Adverse Event Reporting System(FAERS)database in order to provide references for clinical drug safety management.Methods A total of 1 349 trabectedin-related reports were extracted from the FAERS database from Q1 2007 to Q4 2024.Using the MedDRA coding classification system for system organ class(SOC)and preferred term(PT),signal detection was performed through 4 proportional imbalance methods,including reporting odds ratio(ROR)and proportional reporting ratio(PRR).Subgroup analyses by gender,age,and temporal trends were also conducted.Results Hematological and lymphatic system disorders and hepatobiliary system disorders were the primary SOCs involved.High-frequency PTs included neutropenia(123 cases)and anemia(117 cases).Eight potential ADEs that have not been listed in the drug product instruction were identified.The median onset time of ADEs was 21 d,showing an early failure pattern,with differences observed by gender(females more prone to hematological toxicity)and age(elderly more susceptible to febrile neutropenia).Conclusion Trabectedin requires close attention to hematological toxicity,hepatotoxicity,and newly identified multi-system potential risks.Clinically,monitoring should be strengthened based on time windows and population characteristics to optimize drug regimens.Countermeasure It is recommended to strengthen the full cycle monitoring of anti-tumor drugs,standardize the reporting of adverse reactions,and establish a multi-departmental collaborative research platform.

Aim To study the effect of maternal high-fat diet during pregnancy on endothelial to mesenchymal transition of aortic vessels in adult offspring.Methods The pregnant mice were randomly divided into normal diet group and high-fat diet group,and the offspring mice were fed normally for 16 weeks after the mother gave birth.Western blot and RT-qPCR were used to detect the expression and transcription of related proteins,and immunofluorescence and im-munohistochemical staining were used for pathological analysis.Results Compared with the offspring of maternal nor-mal diet during pregnancy,the expressions of vascular inflammatory factors,macrophage infiltration,monocyte-endothelium adhesion were significantly increased in the offspring of maternal high-fat diet(OHF)during pregnancy(P＜0.05).Vas-cular endothelial nitric oxide synthase(eNOS)activity,nitric oxide(NO)level were dramatically reduced(P＜0.05).Immunofluorescence results showed reduced endothelial cell marker CD31 and increased mesenchymal marker α-smooth muscle actin(α-SMA)in OHF.Western blot analysis further confirmed the results,which showed that maternal high fat diet reduced vascular endothelial-cadherin(VE-cadherin)and CD31 and increased α-SMA and Vimentin in the offspring(P＜0.05).The maternal high fat diet increased the extracellular matrix protein disposition and transforming growth factor beta(TGF-β)/Smad signaling in endothelium(P＜0.05).Moreover,the maternal high fat diet reduced Kruppel-like factor 2(KLF2)expression by 76％in mRNA level and 59％in protein level(P＜0.05).Conclusion Maternal high-fat diet during pregnancy lead to a transition of endothelial to mesenchyme in the offspring aorta.The results provide a clue for prevention of vascular disease in early stage.

Fusobacterium nucleatum is an opportunistic pathogenic bacterium that can be enriched in colorectal cancer tissues, affecting multiple stages of colorectal cancer development. The two-component system plays an important role in the regulation and expression of genes related to pathogenic resistance and pathogenicity. In this paper, we focused on the CarRS two-component system of F. nucleatum, and the histidine kinase protein CarS was recombinantly expressed and characterized. Several online software such as SMART, CCTOP and AlphaFold2 were used to predict the secondary and tertiary structure of the CarS protein. The results showed that CarS is a membrane protein with two transmembrane helices and contains 9 α-helices and 12 β-folds. CarS protein is composed of two domains, one is the N-terminal transmembrane domain (amino acids 1-170), the other is the C-terminal intracellular domain. The latter is composed of a signal receiving domain (histidine kinases, adenylyl cyclases, methyl-accepting proteins, prokaryotic signaling proteins, HAMP), a phosphate receptor domain (histidine kinase domain, HisKA), and a histidine kinase catalytic domain (histidine kinase-like ATPase catalytic domain, HATPase_c). Since the full-length CarS protein could not be expressed in host cells, a fusion expression vector pET-28a(+)-MBP-TEV-CarS_cyto was constructed based on the characteristics of secondary and tertiary structures, and overexpressed in Escherichia coli BL21-Codonplus(DE3)RIL. CarS_cyto-MBP protein was purified by affinity chromatography, ion-exchange chromatography, and gel filtration chromatography with a final concentration of 20 mg/ml. CarS_cyto-MBP protein showed both protein kinase and phosphotransferase activities, and the MBP tag had no effect on the function of CarS_cyto protein. The above results provide a basis for in-depth analysis of the biological function of the CarRS two-component system in F. nucleatum.
Humans ; Histidine Kinase/metabolism* ; Fusobacterium nucleatum/metabolism* ; Automobiles ; Protein Kinases/genetics* ; Escherichia coli/metabolism* ; Colorectal Neoplasms

Objective To investigate the feasibility of sequential intensity-modulated radiotherapy (sIMRT)and simultaneously integrated boost intensity-modulated radiotherapy(SIB-IMRT)in the radiotherapy of brain metastasis,the dosimetric difference of target volumes and organs at risk(OARs). Methods Twenty pa-tients diagnosed as brain metastasis were randomly selected,with SIB-IMRT and sIMRT programs developed for each patient. Dosimetric differences between target areas and OARs were compared between the two radiotherapy protocols. Results Compared with sIMRT,SIB-IMRT had no significant difference in the average irradiation dose of the brainstem[(42.69 ± 2.18)Gy vs.(41.98 ± 0.96)Gy]and homogeneity index(HI)(1.46 ± 0.04 vs.1.42 ± 0.13)of P-CTV(P > 0.05). However,SIB-IMRT plan achieved higher than sIMRT in the conformation index (CI)(0.68 ± 0.05 vs. 0.44 ± 0.04)and HI(1.03 ± 0.01 vs. 1.06 ± 0.01)of P-GTV. Meanwhile,both maximum exposure dose of OARs and CI of P-CTV(0.68 ± 0.05 vs.0.44 ± 0.04)of SIB-IMRT were significant in comparison with sIMRT(P<0.05).Conclusions Both radiotherapies can meet target coverage and dose requirements.Com-pared to sIMRT technique,SIB-IMRT technique can decrease effectively the exposure dose of surrounding organs, and can give the tumor target more uniform physical dose conformation.

Aim To study the therapeutic effect of CpG-ODN, an agonist of Toll-like receptor 9 (TLR9), on hypoxic/ischemic encephapathy in neonatal rats and investigate the mechanisms.Methods Fifty healthy 7-day-old neonatal Wistar rats (in either gender, weighing 12~17g) were randomly divided into sham operation group, HIBD group, and CpG-ODN low group(0.35 mL·kg-1), CpG-ODN middle group(1.40 mL·kg-1), CpG-ODN high group(5.60 mL·kg-1).The neurological function was scored after 48h operation;ten rats of each group was executed respectively and brains tissue was taken;HE staining was used to observe the brain pathological changes.Western blot assay was used to detect the expressions of TLR9 and phosphor-p38 mitogen-activated protein kinases(p-p38 MAPK), and enzyme linked immunosorbent assay (ELISA) method was adopted to detect TNF-α expression.Results The CpG-ODN low, middle group were improved in impairment significantly compared with the HIBD group, and the brain pathological change was lessened, while the CpG-ODN high group was impaired significantly compared with the HIBD group (P<0.05), and brain pathological change was sharpened.Western blot showed the up-regulation in TLR9 and p-p38 MAPK and a significant increase of the expression of TNF-α in the brain tissue in CpG-ODN group with statistical difference in HIBD group and sham operation group(P<0.05).Conclusions The neuro-behavioral score and nervous system function can be improved and the hypoxic/ischemic brain damage can be reduced in neonatal rats in the CpG-ODN low, middle group.The protective mechanisms may be suitably via activating p38 MAPK signaling pathway to promote p38 MAPK phosphory1ation and up-regulation of the expression of TNF-α in the brain tissue of rats.

Objective To evaluate the therapeutic efficacy of percutaneous transhepatic portal vein balloon angioplasty in treating cavernous transformation of portal vein following operation of congenital choledochal cyst. Methods From 2012 to 2014, a total of 6 patients with cavernous transformation of portal vein which occurred after the operation of congenital choledochal cyst were encountered at authors’ hospital. The clinical data were retrospectively analyzed. Before treatment, all patients presented symptoms of different degrees of hematemesis. Percutaneous transhepatic portal vein balloon angioplasty was carried out in all patients, and embolization of gastric coronary vein with coils was employed if angiography showed that coronary vein of stomach was pronouncedly dilated. The clinical manifestations, the imaging materials and the complications were analyzed. All the patients were followed up for 3 - 31 months. Results Of the 6 patients, portal vein main stem occlusion was found in 5 and severe localized stenosis was seen in one. Cavernous transformation of portal vein was revealed in all the 6 patients. Percutaneous transhepatic portal vein balloon angioplasty was successfully accomplished in 5 patients and failed in one patient. Embolization of gastric coronary vein with coils was performed in two patients. After the treatment, no treatment-related severe complications occurred in all patients. The follow-up period ranged from 3 to 31 months. During the follow-up period portal vein maintained patent in 5 patients. No recurrent hematemesis occurred in all patients. Conclusion For the treatment of cavernous transformation of portal vein occurring after the operation of congenital choledochal cyst, percutaneous transhepatic portal vein balloon angioplasty is a safe, effective and minimally - invasive therapeutic means.

ObjectiveTo establish an animal model of implanted inferior vena cava tumor thrombus (IVCTT)and examine its growth with MDCT and 3D-MPR. MethodsTumor cell line VX2 was inoculated subcutaneously into rabbit to develop the primary tumor, which was then cut into small strips. Purse-string suture was performed on the anterior wall of IVC after the laparotomy in eighteen New Zealand white rabbits.The tumor strip was injected into IVC through the purse and suspensory fixed on the inner wall of IVC. The general conditions,body weight,and the survival time were monitored after operations.MDCT examinations were performed with plain scan,arterial phase,portal phase and venous phase enhancement every week for all animals and 3D-MPR were acquired.The volumes of IVCTT were calculated.IVC,IVCTT and metastasis were examined with gross and histological pathology. ResultsThe IVCTT was confirmed by MDCT and 3D-MPR images.Collateral varicose veins caused by IVC obstruction and metastasis were also shown in images.IVCTT and metastasis were confirmed by pathological method. The success rate of IVCTT was 100 ％. The mean survival time of operated animals was(49.5±4.4)days. ConclusionsInjecting and suspensory fixing VX2 tumor strip into IVC is a reliable method to establish the IVCTT animal model. MDCT and 3D-MPR are valuable methods to monitor the growth and metastasis of IVCTT in animal models. The model of implanted IVCTT of rabbits provides a useful tool for the research of treatment of IVCTT.