Aim To explore the feasibility of the cloud exposure system for in vitro exposure experiments on inhalation toxicology.Methods Calu-3 cells cultured at the air-liquid interface(ALI)were exposed to three concentrations of lipopolysaccha-ride(LPS):high,medium,and low(800,400,200 mg·L-1)by the cloud exposure system,and phosphate buffer solu-tion(PBS)was used as a negative control group for one expo-sure,while the high concentration of LPS was used to expose Calu-3 cells for five times.Calu-3 cells were exposed to phos-phate buffer solution(PBS)once as negative control group and to high concentration of LPS solution for five times,and the ac-tivity of Calu-3 cells,the release of lactate dehydrogenase(LDH),TEER,mucin MUC5AC,and the expression of inflam-matory factors IL-6,IL-8 and TNF-α were detected 3 h and 24 h after the end of the exposure,respectively.Results Compared with the PBS-negative control group,after exposure to the Calu-3 cell model at the air-liquid interface with three concentrations of LPS,high,medium,and low,there were no significant changes in the activity and LDH release,but the cellular electrical resist-ance value was reduced,and the barrier function of the cells was impaired;with the increase of the exposure concentration,the LPS promoted the expression of the cellular mucin MUC5AC,which led to a decrease in the expression of cellular IL-6,IL-8,and a decrease in the expression of TNF-α.Expression of IL-6 and IL-8 decreased and TNF-α expression increased;as the fre-quency of exposure increased,LPS inhibited the expression of mucin and increased the expression of IL-6;an increase in the frequency of exposure along with a prolongation of post-exposure assay time resulted in an increase in the expression of cellular IL-8 and TNF-a.Conclusions The ALI cloud exposure ap-proach can effectively reflect the cellular response to positive subjects,and this in vitro exposure can be used in subsequent exposure experiments to evaluate the inhalation toxicity of com-pounds.

Objectives: . Our study aimed to explore the role of the potassium channel KCNK1 in head and neck squamous cell carcinoma, focusing on its impact on tumor growth, invasion, and metastasis. We also investigated the therapeutic potential of quinidine, a known KCNK1 inhibitor, in both in vitro cell lines and a zebrafish patient-derived xenograft (PDX) model. Methods: . We established primary cell cultures from head and neck cancer tissues and employed the FaDu cell line for in vitro studies, modulating KCNK1 expression through overexpression and knockdown techniques. We evaluated cell migration, invasion, and proliferation. Additionally, we developed a zebrafish PDX model to assess the impact of quinidine on tumor growth and metastasis in vivo. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to elucidate the molecular mechanisms underlying the role of KCNK1 in cancer progression. Results: . Overexpression of KCNK1 in FaDu cells resulted in enhanced cell migration and invasion, whereas its knockdown diminished these processes. In the zebrafish PDX model, quinidine markedly inhibited tumor growth and metastasis, demonstrating a significant reduction in tumor volume and micrometastasis rates compared to the control groups. The molecular analyses indicated that KCNK1 plays a role in critical signaling pathways associated with tumor growth, such as the Ras and MAPK pathways. Conclusion . Our findings highlight the critical role of KCNK1 in promoting tumor growth and metastasis in head and neck cancer. The inhibitory effect of quinidine on tumor progression in the zebrafish PDX model highlights the therapeutic potential of targeting KCNK1. These results suggest that KCNK1 could serve as a valuable therapeutic target for head and neck cancer, warranting further investigation into treatments that target KCNK1.

Objectives: . Our study aimed to explore the role of the potassium channel KCNK1 in head and neck squamous cell carcinoma, focusing on its impact on tumor growth, invasion, and metastasis. We also investigated the therapeutic potential of quinidine, a known KCNK1 inhibitor, in both in vitro cell lines and a zebrafish patient-derived xenograft (PDX) model. Methods: . We established primary cell cultures from head and neck cancer tissues and employed the FaDu cell line for in vitro studies, modulating KCNK1 expression through overexpression and knockdown techniques. We evaluated cell migration, invasion, and proliferation. Additionally, we developed a zebrafish PDX model to assess the impact of quinidine on tumor growth and metastasis in vivo. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to elucidate the molecular mechanisms underlying the role of KCNK1 in cancer progression. Results: . Overexpression of KCNK1 in FaDu cells resulted in enhanced cell migration and invasion, whereas its knockdown diminished these processes. In the zebrafish PDX model, quinidine markedly inhibited tumor growth and metastasis, demonstrating a significant reduction in tumor volume and micrometastasis rates compared to the control groups. The molecular analyses indicated that KCNK1 plays a role in critical signaling pathways associated with tumor growth, such as the Ras and MAPK pathways. Conclusion . Our findings highlight the critical role of KCNK1 in promoting tumor growth and metastasis in head and neck cancer. The inhibitory effect of quinidine on tumor progression in the zebrafish PDX model highlights the therapeutic potential of targeting KCNK1. These results suggest that KCNK1 could serve as a valuable therapeutic target for head and neck cancer, warranting further investigation into treatments that target KCNK1.

Objectives: . Our study aimed to explore the role of the potassium channel KCNK1 in head and neck squamous cell carcinoma, focusing on its impact on tumor growth, invasion, and metastasis. We also investigated the therapeutic potential of quinidine, a known KCNK1 inhibitor, in both in vitro cell lines and a zebrafish patient-derived xenograft (PDX) model. Methods: . We established primary cell cultures from head and neck cancer tissues and employed the FaDu cell line for in vitro studies, modulating KCNK1 expression through overexpression and knockdown techniques. We evaluated cell migration, invasion, and proliferation. Additionally, we developed a zebrafish PDX model to assess the impact of quinidine on tumor growth and metastasis in vivo. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to elucidate the molecular mechanisms underlying the role of KCNK1 in cancer progression. Results: . Overexpression of KCNK1 in FaDu cells resulted in enhanced cell migration and invasion, whereas its knockdown diminished these processes. In the zebrafish PDX model, quinidine markedly inhibited tumor growth and metastasis, demonstrating a significant reduction in tumor volume and micrometastasis rates compared to the control groups. The molecular analyses indicated that KCNK1 plays a role in critical signaling pathways associated with tumor growth, such as the Ras and MAPK pathways. Conclusion . Our findings highlight the critical role of KCNK1 in promoting tumor growth and metastasis in head and neck cancer. The inhibitory effect of quinidine on tumor progression in the zebrafish PDX model highlights the therapeutic potential of targeting KCNK1. These results suggest that KCNK1 could serve as a valuable therapeutic target for head and neck cancer, warranting further investigation into treatments that target KCNK1.

Purpose: This study was conducted to evaluate the efficacy of bladder outlet surgery in patients with detrusor underactivity (DU) and to identify factors associated with successful outcomes. Methods: We conducted a retrospective review of men diagnosed with DU in urodynamic studies who underwent bladder outlet surgery for lower urinary tract symptoms between May 2018 and April 2023. The International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry (UFM), and multichannel urodynamic studies were administered. Successful treatment outcomes were defined as either an IPSS improvement of at least 50% or the regaining of spontaneous voiding in patients urethral catheterization prior to surgery. Results: The study included 93 male patients. Men diagnosed with significant or equivocal bladder outlet obstruction (BOO) experienced significant postoperative improvements in IPSS (from 20.6 to 6.0 and from 17.4 to 6.5, respectively), maximum urine flow rate (from 5.0 mL/sec to 14.4 mL/sec and from 8.8 mL/sec to 12.2 mL/sec, respectively) and voiding efficiency (from 48.8% to 86.0% and from 61.2% to 85.1%, respectively). However, in the group without obstruction, the improvements in IPSS and UFM results were not significant. The presence of detrusor overactivity (odds ratio [OR], 3.152; P=0.025) and preoperative urinary catheterization (OR, 2.756; P=0.040) were associated with favorable treatment outcomes. Conversely, an unobstructed bladder outlet was identified as a negative prognostic factor. Conclusions In men with DU accompanied by equivocal or significant BOO, surgical intervention to alleviate the obstruction may enhance the IPSS, quality of life, and UFM results. However, those with DU and an unobstructed bladder outlet face a comparatively high risk of treatment failure. Preoperative detrusor overactivity and urinary catheterization are associated with more favorable surgical outcomes. Consequently, active deobstructive surgery should be considered for patients with DU who are experiencing urinary retention.

Objective: To examine the application value of 3D Slicer software assisted domestic frameless stereotactic robot in biopsy of intracranial lesions. Methods: A retrospective analysis was performed on 80 patients who admitted consecutively and underwent intracerebral lesions biopsy with the domestic frameless stereotactic robot at Department of Neurosurgery, Aerospace Central Hospital from January 2019 to December 2021. There were 36 males and 44 females, with a mean age of (38.5±18.0) years (range: 6 to 71 years). Before surgery only enhanced T1-weighted three-dimensional magnetization prepared gradient echo sequences and diffusion tensor imaging scans were performed. Self-reconstruction of intracranial lesions, cerebral cortex and blood vessels was carried out using 3D Slicer software system after the DICOM format imaging data of 80 patients were collected. These imaging data were merged to the workstation of the domestic frameless stereotactic robot for preoperative surgical planning and the surgical puncture path was designed to avoid blood vessels in the brain functional area, cerebral cortex and sulcus. Results: All frameless stereotactic biopsy were successfully performed. Postoperative pathological diagnosis included 50 cases of diffuse astrocytic and oligodendroglioma, 15 cases of lymphoma, 5 cases of metastatic tumors, 5 cases of inflammatory demyelinating disease, 2 cases of inflammatory granuloma, 1 case of hemangioma, 1 case of acute lymphoblastic leukemia intracranial invasion and 1 case of seminoma. The positive diagnosis rate was 100% (80/80). Postoperative imaging confirmed that the puncture path and target were accurately implemented according to the preoperative planning, and the target error was (1.32±0.44) mm (range: 0.55 to 1.99 mm). One case of puncture-related bleeding occurred at the target after surgery and improved after treatment. Conclusion: The three-dimensional multimodal images reconstructed by the 3D Slicer software before operation could help the surgeons make the preoperative planning and reduce the risk of stereotactic brain biopsy.
Male ; Female ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Brain Neoplasms/pathology* ; Diffusion Tensor Imaging ; Retrospective Studies ; Robotics ; Biopsy ; Software ; Stereotaxic Techniques

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

Humans ; Child ; Neurofibromatosis 1/drug therapy* ; Benzimidazoles/therapeutic use*

Objective: To evaluate the efficacy of supraclavicular fasciocutaneous island flap (SIF) for repairing the defect of parotid or auricle regions after tumor resection. Methods: From February 2019 to June 2021, 12 patients (11 males and 1 female, aged 54-77 years old), of whom 4 with parotid adenoid cystic carcinoma and 8 with auricular basal cell carcinoma underwent reconstruction surgery for postoperative defects in the parotid gland area and auricular area with SIF in the Department of Otorhinolaryngology Head and Neck Surgery, the Second Xiangya Hospital of Central South University and their clinical data were retrospectively analyzed. Size of the SIF, time for harvesting SIF, neck lymph node dissection and postoperative complications were recorded. Results: The flap areas were (6-9) cm × (8-13) cm, and the harvesting time for SIF ranged from 40 to 80 min, averaging 51.7 min. The donor sites were directly closed. All patients underwent ipsilateral levels Ⅰ-Ⅲ neck dissection, with 4 cases undergoing additional level Ⅳ neck dissection and 2 cases undergoing level Ⅳ-Ⅴ neck dissection. Of the 12 SIF, 10 were completely survival and 2 had flap arterial crisis with partial flap necrosis, in addition, 1 had donor site wound dehiscence. With follow-up of 10-42 months, there were no tumor recurrences in 10 patients, 1 patient was lost to follow-up at 10 months postoperatively, and 1 patient experienced local tumor recurrence at 11 months after surgery and died 15 months later. Conclusion: SIF is an easily harvested flap with good skin features matching the skin in parotid and auricle regions and less damage to donor site, and this flap has no need for microvascular anastomosis technique. SIF is feasible and effective for repairing defects in parotid and auricle area.
Male ; Humans ; Female ; Middle Aged ; Aged ; Plastic Surgery Procedures ; Parotid Gland/surgery* ; Retrospective Studies ; Neoplasm Recurrence, Local ; Surgical Flaps/blood supply* ; Skin Transplantation/methods* ; Postoperative Complications ; Treatment Outcome

Humans ; Otolaryngology ; Head/surgery* ; Neck/surgery*