Objective: To describe a technique of endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma, based on anatomic studies and surgeries. Methods: Three dry human skulls and five fresh human cadaver heads were used for anatomic study of a endoscopic transoral approach to expose petroclival and jugular foramen. The anatomical landmarks and the extent of exposure were recorded. Six clinical cases who were treated in Eye & ENT Hospital, Fudan University from June 2020 to April 2022 were used to illustrate the technique and feasibility of this approach and to assess its indications and advantages, including 3 males and 3 females, aged 42 to 69 years old. Descriptive analysis was used in this research. Results: On the basis of the preservation of the internal pterygoid muscle and the external pterygoid muscle, this approach could fully expose the parapharyngeal, petrosal and paraclival segment internal carotid arteries, and safely deal with the lesions of jugular foramen and petroclival region. The 6 patients in our study tolerated the procedure well. Postoperative enhanced MRI showed complete resection of the tumor and no postoperative masticatory dysfunction. Conclusion: Endoscopic transoral approach is a safe, minimally invasive and effective surgical treatment for petroclival and jugular foramen recurrent nasopharyngeal carcinoma.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Nasopharyngeal Carcinoma ; Jugular Foramina ; Neoplasm Recurrence, Local ; Endoscopy/methods* ; Nasopharyngeal Neoplasms/surgery*

Humans ; Endoscopy ; Neurosurgical Procedures ; Skull Base/surgery*

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Up-frameshift 1 (UPF1), as the most critical factor in nonsense-mediated messenger RNA (mRNA) decay (NMD), regulates tumor-associated molecular pathways in many cancers. However, the role of UPF1 in lung adenocarcinoma (LUAD) amino acid metabolism remains largely unknown. In this study, we found that UPF1 was significantly correlated with a portion of amino acid metabolic pathways in LUAD by integrating bioinformatics and metabolomics. We further confirmed that UPF1 knockdown inhibited activating transcription factor 4 (ATF4) and Ser51 phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), the core proteins in amino acid metabolism reprogramming. In addition, UPF1 promotes cell proliferation by increasing the amino-acid levels of LUAD cells, which depends on the function of ATF4. Clinically, UPF1 mRNA expression is abnormal in LUAD tissues, and higher expression of UPF1 and ATF4 was significantly correlated with poor overall survival (OS) in LUAD patients. Our findings reveal that UPF1 is a potential regulator of tumor-associated amino acid metabolism and may be a therapeutic target for LUAD.
Activating Transcription Factor 4/genetics* ; Adenocarcinoma of Lung ; Amino Acids ; Cell Proliferation ; Eukaryotic Initiation Factor-2 ; Humans ; Lung Neoplasms ; RNA Helicases/metabolism* ; RNA, Messenger/metabolism* ; Trans-Activators/metabolism*

Objective: To summarize the application of temporalis muscle flap in the salvage nasopharyngectomy for advanced recurrent nasopharyngeal carcinoma (rNPC), and to provide guidance for the repair of extensive skull base defects in salvage rNPC. Methods: A total of 54 patients with the application of temporalis muscle flap in the salvage nasopharyngectomy for advanced rNPC were retrospectively analyzed, including 42 males and 12 females, aging from 29 to 71 years. There were 36 patients with rT3 and 18 patients with rT4. The surgical methods of temporalis muscle flap repair were summarized. The general situation, survival time and postoperative complications of patients were recorded, and the advantages and disadvantages of temporalis muscle flap were discussed. Results: The temporal muscle flap could completely cover the defect area of nasopharynx and skull base, without the need for other autologous repair materials. The follow-up period was 2 to 28 months. The survival rate of temporalis flap was 98.1% (53/54). The 1-year overall survival rate was 84.5% while 1-year progression-free survival rate was 49.0%. None of the patients had facial nerve injury. Three patients (5.6%) had necrosis of the cranial membrane required surgical intervention and four patients (7.4%) required a chonoplasty due to severe chonostril stenosis or chonostril atresia. Eleven cases (20.4%) had mouth opening restriction, chewing weakness, dysphagia and other eating difficulties. Conclusions: Temporalis muscle flap is an alternative flap for the salvage nasopharyngectomy for advanced rNPC. Temporal muscle flap shows high survival rate and wide coverage, but the surgeon should apprehend the possible complications and reduce the occurrence of them.
Humans ; Male ; Female ; Nasopharyngeal Carcinoma ; Retrospective Studies ; Surgical Flaps ; Nasopharyngeal Neoplasms/pathology* ; Muscles/pathology*

Objective: To evaluate the efficiency of internal carotid artery (ICA) embolization technology in endoscopic salvage surgery for recurrent nasopharyngeal carcinoma (rNPC) invading the ICA. Methods: From January 2016 to March 2021, 83 patients with rNPC who invaded the ICA and underwent endoscopic extended nasopharyngectomy were retrospectively collected from the Eye & ENT Hospital in Fudan University, including 60 males and 23 females. The age of the patients ranged from 27 to 77 years. The standard of ICA invasion was that the distance from the lesion to the ICA on enhanced MRI was ≤ 1.8 mm. The clinical characteristics, ICA management strategy and survival prognosis of patients were analyzed, and the effectiveness of ICA embolization was evaluated. Kaplan-Meier method was used to calculate the survival rate and Log-rank test was used to compare the difference. Results: In 83 patients with rNPC, there were 13 patients with rT2, 38 patients with rT3, 32 patients with rT4, and 16 patients had lymph node metastasis. A total of 37 patients (44.6%) underwent ICA coil embolization before surgery, of which 2 cases underwent external carotid-middle cerebral artery artery bypass grafting and ICA embolization due to positive balloon occlusion test (BOT). Patients with positive surgical margin accounted for 24.1% (20/83). Among them, patients with rT4 and patients without ICA embolization had a higher positive rate of surgical margin (P value was 0.001, 0.043, respectively). The 3-year overall survival (OS) and progression free survival (PFS) rate of all patients was 46.5% and 26.7%, respectively. In addition, the 3-year OS and PFS of patients with ICA embolization was significantly higher than those without ICA embolization, respectively (69.1% vs 27.8%, P=0.003; 33.9% vs 18.9%, P=0.018). Only 2 patients (2/37, 5.4%) had cerebral infarction complications after coil embolization of the affected ICA due to negative BOT. Conclusion: Preoperative ICA embolization can be used to treat patients with rNPC invading the ICA, improve the total removal rate and survival rate of patients, which is an effective salvage treatment.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Nasopharyngeal Carcinoma ; Salvage Therapy ; Retrospective Studies ; Carotid Artery, Internal ; Neoplasm Recurrence, Local/surgery* ; Nasopharyngeal Neoplasms/pathology*

Objective: To evaluate the feasibility of the endoscopic transnasal approach (ETA) and to analyze the outcomes and factors of this surgical technique in the management of the tumor invading the anterior skull base. Methods: A retrospective analysis was performed on 42 patients (31 males and 11 females, with mean age of 49 years) with sinonasal tumor invading the anterior skull base, who underwent ETA from June 2015 to April 2019 in Eye, Ear, Nose and Throat Hospital of Fudan University. Pathologically, there were 15 cases of squamous carcinoma (14 patients with T4bN0M0 and 1 patient with T4bN1M0) and 27 of olfactory neuroblastomas with Kadish stage C. Anterior skull base reconstruction was performed using the vascular pedicled nasoseptal mucoperiosteal flap and fascia lata. Brain non-contrast-enhanced CT was performed on the first postoperative day to exclude massive pneumocephalus, relevant brain edema and subarachnoid hemorrhage. Sinonasal contrast-enhanced MR was performed to assess the extent of the tumor removal. Kaplan-Meier analysis was used to calculate the overall survival (OS) and Cox multivariate regression analysis was used to determine the prognostic factors. Results: The mean duration of the surgery was 452 minutes. Total resection was performed in 36 patients (85.7%), subtotal resection in 2 patients (4.8%) with orbital involvement, partial resection in one patient (2.4%) with injury of the internal carotid artery. One patient (2.4%) underwent the second resection because of the tumor residual, two patients (4.8%) with unsure tumor residual. Mean follow-up was 20 months, with 17 months of median follow-up. One-, two-and three-year overall survival was 86.5%, 76.9% and 64.5%, respectively. For squamous carcinoma, one-, two-and three-year overall survival was 86.2%, 86.2% and 57.4%, respectively. For olfactory neuroblastomas, One-, two-and three-year overall survival was 86.9%, 75.3% and 67.8%, respectively. Multivariate analysis showed that tumor residual (P=0.001) and recurrence (P<0.01) were independent prognostic factors for survival. Conclusions: The ETA is safe and feasible in selected patients with sinonasal tumor invading the anterior skull base. Tumor residual and recurrence are independent prognostic factors for survival.
Female ; Humans ; Male ; Middle Aged ; Nasal Cavity ; Neoplasm Recurrence, Local ; Nose Neoplasms/surgery* ; Retrospective Studies ; Skull Base/surgery* ; Skull Base Neoplasms/surgery*

Objective:To explore the protective effects and related mechanism of tea saponin (TS) on intestinal inflammation due to Shigella infection. Methods:In vitro, the antibacterial activity of TS was detected by standard broth microdilution method. The absorbance at 600 nm of the bacterial liquid was detected by Microplate Reader under different concentrations of TS, and the growth curve was drawn. Bacterial count was obtained by plate colony counting. In vivo, 15 mice were divided into 3 groups ( n=5 each): control group, Sf301 group and TS group. Sterile water or TS was applied to mice in the Sf301 group and the TS group per gavage once a day for 8 days, and the mouse model of Shigella infection was established on day 3. The disease activity index (DAI) was used to evaluate the general condition of mice. The mice were sacrificed on day 8. Colon length was measured and colon tissues were stained with HE to analyze the pathological changes. The cecal contents and feces of mice were taken for plate counting and Shigella load was obtained. Real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the mRNA expression levels of inflammatory factors. Results:(1) In vitro, the MIC of TS was 1 024 μg/ml. The plate counting and A600 of TS decreased in proportion to increasing concentrations (256, 512, 1 024 μg/ml) in comparison with the control group (all P<0.05). (2) In vivo, colon length was (7.70±0.24) cm in the control group and (7.35±0.41) cm in the TS group, which was significantly longer than that of the Sf301 group ([6.13±0.05] cm, P<0.05). Histopathological examination evidenced colonic epithelial cells shedding, decreased goblet cells, and inflammatory cell infiltration in the colon tissue of the Sf301 group. In the TS group, the colonic mucosa was intact without significant inflammatory cell infiltration. Bacterial load in cecal contents was significantly lower in the TS group than in the Sf301 group ( P<0.05). The level of tumor necrosis factor-α was significantly lower, and the level of interleukin-10 was significantly higher in the TS group than in the Sf301 group (all P<0.05). Conclusion:TS can effectively inhibit Shigella and alleviate Shigella infective enteritis by reducing Shigella load and inhibiting inflammation.

Allicin is one of the main bioactive substances in garlic, with antibacterial, hypolipidemic and other pharmacological effects. In this study, apoptosis-related indicators were detected to explore the molecular mechanism of allicin on KG-1 cell proliferation inhibition. The apoptosis rate of KG-1 cells induced by allicin was detected by flow cytometry. The effect of allicin on the expressions of Bax, Bcl-2, survivin and ERK mRNA in KG-1 cells was detected by RT-qPCR. Western blot was used to detect the expressions of caspase 3, cleaved caspase 3, ERK1/2, p-ERK1/2 and survivin protein in KG-1 cells. According to the findings, compared with the control group, allicin could significantly inhibit the proliferation activity of KG-1 cells in a concentration-dependent and time-dependent manner. Flow cytometry showed that allicin could induce the apoptosis of KG-1 cells, which was mainly late apoptosis. The results of RT-qPCR showed that the expressions of Bax mRNA, Bcl-2, survivin and ERK mRNA in KG-1 cells increased after treatment with allicin. The results of Western-blot showed that after KG-1 cells were treated with allicin, the expressions of caspase 3 and its active form cleaved caspase 3 increased, the expressions of survivin, ERK1/2 and its active form p-ERK1/2 were decreased, of which p-ERK1/2 was down-regulated in a dose-dependent manner. The above results suggest that allicin inhibited the proliferation of KG-1 cells primarily by inducing late apoptosis; the execution of apoptosis involved cleaved caspase 3; the induction of apoptosis involved the protein expression, the decrease of ERK1/2andexpression of survivin and the dose-dependent decrease of p-ERK1/2; the mRNA expression involved the increase of Bax, and the down-regulation of survivin, Bcl-2 and ERK1/2.

Objective To evaluate the effects of GLYX-13 on cognitive function after long-time isoflurane anesthesia in mice. Methods A total of 192 healthy male C57∕B6J mice, aged 8 weeks, weig-hing 22-25 g, were divided into 4 groups(n=48 each)using a random number table: control group (group C), isoflurane anesthesia group(group I), GLYX-13 group(group G), and isoflurane anesthesia plus GLYX-13 group(group IG). The animals were exposed to 15% isoflurane for 6 h in I and IG groups. GLYX-13 1 mg∕kg was injected via the caudal vein at 2 h before anesthesia in G and IG groups. Novel ob-ject recognition test and contextual fear conditioning test were performed on 1st, 3rd and 7th days after an-esthesia. The expression of 2B subunits-containing NMDA receptor(NR2B)and cyclic adenosine mono-phosphate response element-binding protein(CREB)mRNA in the hippocampus was detected by quantita-tive real-time polymerase chain reaction after the end of behavioral tests on 1st, 3rd and 7th days after anes-thesia. Results Compared with group C, the percentage of time spent in exploring a novel object, dis-crimination index and percentage of freezing time were significantly decreased, and the expression of NR2B and CREB mRNA in the hippocampus was down-regulated in group I(P <005). Compared with group I, the percentage of time spent in exploring a novel object, discrimination index and percentage of freezing time were significantly increased, and the expression of NR2B and CREB mRNA in the hippocampus was up-regulated in group IG(P <005). Conclusion GLYX-13 can significantly improve the cognitive func-tion after long-time isoflurane anesthesia in mice.