Objective:To evaluate the feasibility and outcomes of transnasal endoscopic clipping of the paraclival internal carotid artery (ICA) in skull base surgery.Methods:The paraclival ICA was anatomically dissected in cadaveric head specimens. The clinical data of 15 patients with skull base lesions involving the ICA who admitted to the Department of Otorhinolaryngology Head and Neck Surgery at Tianjin Huanhu Hospital from January 2021 to December 2023 were retrospectively analyzed. Among them, 4 patients underwent transnasal endoscopic clipping of the paraclival ICA and concurrent lesion resection. The surgical methods were summarized, and the key points and indications of this technique were analyzed.Results:Intraoperative clipping of the ICA was successful and hemostatic in all 4 patients. Postoperatively, 3 patients had no complications, while 1 patient developed delayed ischemic cerebral infarction. Two patients were cured, 1 patient was maintained on immunotherapy, and 1 patient died. During follow-up, the clip was in situ in 1 patient, had detached in another, and was obscured by temporal muscle coverage in the remaining 2 patients.Conclusions:Transnasal endoscopic clipping of the paraclival ICA represents a potential option for managing the ICA in skull base surgery. However, it carries significant risks and limitations, mandating careful patient selection based on specific circumstances.

Objective:To evaluate the feasibility and outcomes of transnasal endoscopic clipping of the paraclival internal carotid artery (ICA) in skull base surgery.Methods:The paraclival ICA was anatomically dissected in cadaveric head specimens. The clinical data of 15 patients with skull base lesions involving the ICA who admitted to the Department of Otorhinolaryngology Head and Neck Surgery at Tianjin Huanhu Hospital from January 2021 to December 2023 were retrospectively analyzed. Among them, 4 patients underwent transnasal endoscopic clipping of the paraclival ICA and concurrent lesion resection. The surgical methods were summarized, and the key points and indications of this technique were analyzed.Results:Intraoperative clipping of the ICA was successful and hemostatic in all 4 patients. Postoperatively, 3 patients had no complications, while 1 patient developed delayed ischemic cerebral infarction. Two patients were cured, 1 patient was maintained on immunotherapy, and 1 patient died. During follow-up, the clip was in situ in 1 patient, had detached in another, and was obscured by temporal muscle coverage in the remaining 2 patients.Conclusions:Transnasal endoscopic clipping of the paraclival ICA represents a potential option for managing the ICA in skull base surgery. However, it carries significant risks and limitations, mandating careful patient selection based on specific circumstances.

OBJECTIVE To predict the in vivo bioequivalence of lenvatinib mesilate capsules and reference preparation by using the parallel artificial membrane permeability analysis. METHODS Based on the biopharmaceutics classification system classification of lenvatinib mesilate and the parallel artificial membrane permeation model, the in vitro dissolution permeation rate test model of lenvatinib mesilate capsules was established, through real-time monitoring of the dissolution and penetration of lenvartinib mesylate capsules and reference preparations in fasting gastric juice, intestinal fluid and postprandial intestinal fluid, the flux and total penetration of drugs through the membrane were calculated. RESULTS In fasting state and fed state, the 90% confidence interval of geometric mean ratio of two key quality parameters (permeation flux and permeation amount) of the preparation A all were in the range of 80.00%−125.00%, the preparation B did not fall into this interval. CONCLUSION This research method can predict the bioequivalence of renvartinib mesylate capsule and reference preparation, and has a certain correlation in vivo and in vitro.

BACKGROUND: Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is a key protein that maintains myocardial Ca 2+ homeostasis. The present study aimed to investigate the mechanism underlying the SERCA2a-SUMOylation (small ubiquitin-like modifier) process after ischemia/reperfusion injury (I/RI) in vitro and in vivo . METHODS: Calcium transient and systolic/diastolic function of cardiomyocytes isolated from Serca2a knockout (KO) and wild-type mice with I/RI were compared. SUMO-relevant protein expression and localization were detected by quantitative real-time PCR (RT-qPCR), Western blotting, and immunofluorescence in vitro and in vivo . Serca2a-SUMOylation, infarct size, and cardiac function of Senp1 or Senp2 overexpressed/suppressed adenovirus infected cardiomyocytes, were detected by immunoprecipitation, triphenyltetrazolium chloride (TTC)-Evans blue staining, and echocardiography respectively. RESULTS: The results showed that the changes of Fura-2 fluorescence intensity and contraction amplitude of cardiomyocytes decreased in the I/RI groups and were further reduced in the Serca2a KO + I/RI groups. Senp1 and Senp2 messenger ribose nucleic acid (mRNA) and protein expression levels in vivo and in cardiomyocytes were highest at 6 h and declined at 12 h after I/RI. However, the highest levels in HL-1 cells were recorded at 12 h. Senp2 expression increased in the cytoplasm, unlike that of Senp1. Inhibition of Senp2 protein reversed the I/RI-induced Serca2a-SUMOylation decline, reduced the infarction area, and improved cardiac function, while inhibition of Senp1 protein could not restore the above indicators. CONCLUSION I/RI activated Senp1 and Senp2 protein expression, which promoted Serca2a-deSUMOylation, while inhibition of Senp2 expression reversed Serca2a-SUMOylation and improved cardiac function.
Animals ; Mice ; Calcium/metabolism* ; Cysteine Endopeptidases/metabolism* ; Myocardial Reperfusion Injury/metabolism* ; Myocardium/metabolism* ; Myocytes, Cardiac/metabolism* ; Proteins/metabolism* ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics*

Rats ; Animals ; Myocardial Reperfusion Injury/metabolism* ; Luteolin/metabolism* ; Down-Regulation ; Rats, Sprague-Dawley ; MicroRNAs/metabolism* ; Reperfusion Injury ; Apoptosis

Dental erosion is characterized by progressively destroyed teeth, which has no relation to bacteria but to chemicals. Some internal factors, such as gastroesophageal reflux induced by bulimia, anorexia, gastrointestinal diseases, or drugs, and external factors, such as diet, drugs, and occupational acid exposure, are considered promotive factors for this disease. This article presents a patient suffering from severe dental erosion in the whole dentition, especially in the maxillary teeth, due to gastroesophageal reflux induced by glucocorticoid therapy for optic neuritis. This article discusses the mechanism between optic neuritis glucocorticoid therapy and dental erosion.
Humans ; Glucocorticoids/therapeutic use* ; Tooth Erosion/therapy* ; Gastroesophageal Reflux/complications*

Objective:To investigate the effects of histone deacetylase 3 (HDAC3) on the pyroptosis of breast cancer (BC) cells via regulating miR-625/anti-silencing function 1B (ASF1B) and its mechanism.Methods:The expression level of HDAC3, miR-625 and ASF1B in BC tissue, adjacent normal tissue, BC cell lines (T47D, MCF7 and MDA-MB-231) and human normal breast epithelial cell MCF-10A was detected by qRT-PCR. The expression level of cell pyroptosis related protein NLRP3, Caspase-1 and GSDMD was detected by Western blot. The expression level of IL-18 and IL-1βwere detected by ELISA. ChIP experiment was used to determine the interaction between HDAC3 and miR-625. The dual luciferase reporter assay was used to verifiy the targeted regulation between miR-625 and ASF1B.Results:Compared with adjacent normal tissue and MCF-10A cells, the expression of HDAC3 and ASF1B was increased and the expression of miR-625 was decreased in BC tissue and cells (all P<0.05) . Compared with si-NC group, the protein expression level of NLRP3, Caspase-1 and GSDMD in si-HDAC3 group was increased, and the concentration of IL-18 and IL-1β in cell culture supernatant was increased (all P<0.05) . HDAC3 inhibited the expression of miR-625 by binding to the promoter region of miR-625 ( P<0.05) . Compared with si-HDAC3+miR-NC group, The expression of NLRP3, Caspase-1, GSDMD, IL-18 and IL-1β in si-HDAC3+miR-625 inhibitor group was decreased (all P<0.05) . ASF1B was confirmed as a target gene of miR-625, the level of pyroptosis related factors in si-HDAC3+pcDNA3.1-ASF1B group was significantly lower than that in si-HDAC3 + pcDNA3.1-NC group. Conclusion:HDAC3 up regulates the expression of ASF1B by inhibiting miR-625, and then inhibits BC cell pyroptosis.

Objective To investigate the effect of low-dose arsenious acid solution (As(III)) combined with total particulate matter (TPM) from cigarette smoke on cellular oxidative stress in human lung cancer cell line A549 cells. Methods A549 cells were divided into four groups: negative control group (0.75% DMSO), low dose As(III) group (0.88% μg/mL, 75% DMSO), cigarette smoke TPM group (75 μg/mL), and combined exposure group (75 μg/mL TPM, 0.88 μg/mL As (III)). After 24 hours' exposure, the superoxide dismutase (SOD) level in cell culture medium and intracellular 8-hydroxy-2-deoxyguanosine (8-OHdG) content were detected by ELISA, and intracellular reactive oxygen species (ROS) level was detected by fluorescent probe DCFH-DA. 2×2 factorial design was used to evaluate the interaction. Results Compared with the control group, the level of SOD in the combined exposure group was significantly increased (P<0.05). In addition, the ROS content in the combined exposure group and TPM alone group was significantly increased (P<0.05). The levels of 8-OHdG in the combined exposure group and low-dose As(III) treated group were significantly higher than those in the control group(P<0.05). The results of the factorial analysis showed that low-dose As(III) and TPM had interaction on SOD levels, ROS and 8-OHdG contents in A549 cells. The effects on SOD and ROS were synergistic, while the effect on 8-OHdG was antagonistic. Conclusion Low-dose arsenious acid solution As(III) and TPM in cigarette smoke have interaction on oxidative stress in A549 cells.

In order to understand the current development of cell transformation assay (CTA) and its application in the evaluation of cigarette smoke carcinogenesis, the relevant literatures were analyzed and combed from these two aspects. CTA can evaluate the carcinogenicity of various genotoxic and non-genotoxic carcinogens in a short period of time, and has a strong consistency with the results of animal carcinogenic test. After malignant transformation, the cells show changes in cell morphology, immortalization of cells, disappearance of cell-cell contact inhibition, and the ability to form tumors when injected into animals. The identification methods of transformed cells include transformed cell focus count, agglutination test, soft agar culture and inoculation of nude mice, etc. At present, BALB/c 3T3 cells, Bhas 42 cells and SHE cells are the most widely used cells for CTA. Cigarette smoke is a complex aerosol containing a variety of non-genetic carcinogenic chemicals. Cell transformation tests are often used as an in vitro alternative method to evaluate the carcinogenic effects of cigarette smoke, which is different from the short-term genetic toxicity test. It simulates the long-term state of human smoking induced malignant transformation of cells, through the long-term exposure of cells for several decades, which is closer to the occurrence of cancer caused by human smoking. Therefore, CTA can evaluate the carcinogenicity of cigarette smoke and other tobacco products.

BACKGROUNDNon-small cell lung cancer (NSCLC) is the most common lung malignancy worldwide. The metastatic potential of NSCLC cells has been shown to be associated with the tumor microenvironment, which consists of tumor cells, stroma, blood vessels, immune infiltrates and the extracellular matrix. Fibroblasts can produce numerous extracellular matrix molecules and growth factors. Gefitinib has been evaluated as a first-line treatment in selected patients, and it has shown favorable efficacy especially in NSCLC, but it is not effective for everyone.

METHODSIn this study, we examined the antitumor activity of gefitinib on lung fibroblasts co-cultured of lung cancer cells. A series of co-culture experiments that employed cell counting kit-8 (CCK8), transwells, real-time polymerase chain reaction (RT-PCR) and Western blotting with HFL-1 fibroblasts and A549 human lung carcinoma cells were performed to learn more about tumor cell proliferation, migration and invasion; and to determine any change of epithelial mesenchymal transition (EMT)-associated tumor markers vimentin, matrix metallopro-teinase 2 (MMP2) and chemotaxis cytokines receptor 4 (CXCR4) mRNA levels.

RESULTSA549 cell proliferation in the presence of HFL-1 cells was not significantly increased compared with A549 cells alone, but A549 cell spheroid body formation was increased after co-culture, and treatment with gefitinib increased further. Our study also revealed that fibroblasts attenuated the lung cancer cell inhibition ratio of migration and invasion after gefitinib treatment in vitro. To further study this mechanism, RT-PCR analysis showed that vimentin, MMP2 and CXCR4 mRNA levels were more highly expressed in the lung cancer cells after co-culture, but did not obviously decrease compared with the control cells following gefitinib treatment. This suggests the mechanism by which fibroblasts attenuate gefitinib-induced expression of EMT-associated tumor markers. Finally, our results demonstrated that co-culture with A549 lung cancer cells does not alter the cell cycle distribution of HFL-1 fibroblasts. Furthermore, HFL-1 fibroblasts had no effect on the cell cycle distribution of HFL-1 cells treated with gefitinib.

CONCLUSIONGefitinib has lower anti-tumor activity on A549 lung cancer cells when co-cultured with HFL-1 fibroblasts.

Antineoplastic Agents ; pharmacology ; Carcinoma, Non-Small-Cell Lung ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Coculture Techniques ; Epithelial-Mesenchymal Transition ; drug effects ; Fibroblasts ; cytology ; drug effects ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Quinazolines ; pharmacology