Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Objective:To investigate the effects of the Epley and Semont procedures with varying lateral angles of the head on posterior semicircular canal benign paroxysmal positional vertigo （PC-BPPV）. Methods:A total of 115 patients with unilateral PC-BPPV were randomly divided into five groups: Epley group, Semont group, Semont+10° group, Semont+20° group, and Semont+30° group, with 23 patients in each group. Corresponding reduction treatments were performed. Results:The total effective rates for the Epley group, Semont group, Semont+10° group, Semont+20° group, and Semont+30° group were 95.7% （22/23）, 4.3% （1/23）, 30.4% （7/23）, 52.2% （12/23）, and 87.0% （20/23） respectively. The inefficiencies were 4.3% （1/23）, 95.7% （22/23）, 69.6% （16/23）, 47.8% （11/23）, and 13.0% （3/23）. Statistically significant differences were observed in the total effective rates among the five groups （χ²=54.11, P<0.01）. The total effective rates in the Semont group, Semont+10° group, and Semont+20° group were significantly different from that of the Epley group （P<0.01）, while no statistically significant difference was found between the Semont+30° group and the Epley group （P= 0.608>0.012 5）. Conclusion:Among the four Semont methods with different lateral lying angles, the total effective rate of reduction treatment increased with the elevation of the lateral lying angle on the affected side. The efficacy of the Semont+30° group in treating PC-BPPV was not significantly different from the Epley group's reduction effect, which was markedly superior to that of the other four Semont methods at different angles. Therefore, the Semont+30° reduction technique is recommended for the treatment of PC-BPPV.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Benign Paroxysmal Positional Vertigo/therapy* ; Head ; Posture ; Semicircular Canals/physiopathology* ; Treatment Outcome

Objective To explore the efficiency and safety of trans-sheath intraluminal forceps biopsy under digital subtraction angiography(DSA)guidance for assisting diagnosis of pulmonary artery obstructive diseases.Methods Data of 16 patients who underwent trans-sheath intraluminal forceps biopsy for pulmonary artery obstructive diseases were retrospectively analyzed,and the clinical manifestations were recorded.The technical success of biopsy was defined as tissue obtained met the needs of pathology diagnosis.For patients with malignant pathology results,the final diagnosis was malignant,for those with benign pathology results after biopsy and no obvious changes after 6-month or longer follow-up,or benign pathology results after surgical resection,the final diagnosis was benign,otherwise was no clear diagnosis.The operation time,technical success rate,diagnostic efficiency,complications and changes of pulmonary artery pressure before and after the biopsy were observed.Results Among 16 patients,9 complained of intermittent chest tightness,4 complained of chest pain with chest tightness,2 complained of chest pain but 1 denied any symptoms.The lesions located in the left lung in 10 cases and in the right lung in 6 cases,all with enhanced CT showed filling defects of the involved branch of pulmonary artery.Totally 16 trans-sheath intraluminal forceps biopsies were performed in 16 patients,with an average operation time of(31.02±6.02)min and technical success rate of 100%.Malignant tumors were finally diagnosed in 10 cases,including 1 case of lung cancer with false-negative biopsy result,while biopsy correctly diagnosed benign lesions in the other 6 cases.Transient worsening chest pain with chest tightness occurred in 2 cases and relieved after symptomatic treatments.No statistically significant difference of pulmonary artery pressure was found before([53.38±14.28]mmHg)and after([53.69±14.15]mmHg)biopsy(P＞0.05).Conclusion DSA-guided trans-sheath intraluminal forceps biopsy was relatively safe and valuable for assisting diagnosis of pulmonary artery obstructive diseases.

Objective To observe the feasibility and effectiveness of fluoroscopy-guided Fustar adjustable bent sheath clamp biopsy for diagnosing obstructive esophageal diseases.Methods Totally 29 patients with esophageal or esophagogastric junction obstruction who failed to complete endoscopic biopsy were retrospectively analyzed.Real-time fluoroscopy-guided clamp biopsy of lesion areas were performed through 10F Fustar adjustable bent sheath under local anesthesia.The technical success rate,operation time,radiation dose were recorded,and the complications were evaluated.Results Clamp biopsy of lesion areas were successfully performed in all 29 cases,with technical success rate of 100%(29/29),the average operation time of(29.81±10.05)min and the average radiation dose of(127.14±100.36)mGy.No serious complication such as esophageal perforation nor massive bleeding occurred.After biopsy,22 cases(22/29,75.86%)were preliminarily diagnosed as positive,among them 2 cases underwent surgical operation,and the postoperative pathological results were consistent with biopsy.Negative biopsy results were found in 7 cases(7/29,24.14%),among them 2 cases underwent clamp biopsy again 3 months later which showed positive results.Conclusion Fustar adjustable bent sheath clamp biopsy was feasible and effective for diagnosing obstructive esophageal diseases,which could be regarded as the substitution and supplementation of endoscopic clamp biopsy.

Objective To evaluate the efficacy of microwave ablation(MWA)synchronously with biopsy for pulmonary nodules.Methods The data of 64 patients with MWA combined with biopsy were analyzed retrospectively.Thirty-one patients(non-synchronous group)were treated with ablation following biopsy in turn to identify malignant tumors,and 33 patients(synchronous group)were treated by ablation and biopsy synchronously.The technical success rate,operation time,complications,hospitalization time and expenses were compared between non-synchronous group and synchronous group.Results The technical success rate,pneumothorax,and pleural effusion rate showed no significance between the two groups(P>0.05).There were all significant differences in operation time(42.00 min vs 54.26 min),hospitalization time(5.09 days vs 9.26 days),hospitalization expenses(26 840.61 yuan vs 32 527.26 yuan),lung hemorrhage(27.27%vs 87.10%)and hemoptysis(3.03%vs 19.35%)between synchronous group and non-synchronous group,respectively(P<0.05).Conclusion MWA synchronously with biopsy for pulmonary nodules is safe and feasible,which can reduce intraoperative bleeding,shorten treatment period and reduce hospitalization expenses.