ACYP2 functions as an innovative nano-therapeutic target to impede the progression of hepatocellular carcinoma by inhibiting the activity of TERT and the KCNN4/ERK pathway.

An increasing body of evidence suggests that acylphosphatase-2 (ACYP2) polymorphisms are correlated with an increased susceptibility to a range of malignancies. Nevertheless, its potential functions, molecular mechanisms in hepatocellular carcinoma (HCC) and whether it can be act as a therapeutic target remain uninvestigated. Herein, ACYP2 was found to be lowly expressed in HCC and was negatively correlated with tumor size, tumor differentiation, microvascular invasion and the prognosis of HCC patients. Functional investigations revealed that overexpression of ACYP2 inhibited the proliferation and metastasis of HCC cells while promoting apoptosis; knockdown of ACYP2 had the exact opposite effect. Additionally, it was observed that ACYP2 was distributed in both the cytoplasm and nucleus of HCC cells. According to the mechanistic studies, the expression of potassium calcium-activated channel subfamily N member 4 (KCNN4) was negatively regulated by cytoplasmic ACYP2, resulting in the inhibition of K+ outflow and subsequent inactivation of the ERK pathway, which impeded the growth and metastasis of HCC. Furthermore, the activity of telomerase reverse transcriptase (TERT) was inhibited by nuclear ACYP2, leading to the reduction in length of telomeres and consequent reversal of HCC cell immortalization. Additionally, a novel targeted nanotherapy strategy was developed wherein the pcDNA-ACYP2 vector was encapsulated within polyetherimide nanoparticles (PEI/NPs), which were subsequently coated with HCC cell membranes (namely pcDNA/PEI/NPs@M). Safety and targeting characteristics abound for these nanocomposites, in both subcutaneous graft tumor models and orthotopic mouse models, they inhibited the progression of HCC by impeding TERT activity and the KCNN4/ERK pathway. In conclusion, our research identifies novel molecular mechanisms involving cytoplasmic and nuclear ACYP2 that inhibit the progression of HCC. Moreover, pcDNA/PEI/NPs@M represents a targeted therapeutic strategy for HCC that holds great promising.

Excising or preserving perforation margins in endoscopic transtympanic cartilage myringoplasty does not affect surgical success.

OBJECTIVE: To compare the outcome of endoscopic transtympanic cartilage myringoplasty with and without removal of perforation edges for repairing chronic perforations with mucosal chronic otitis media (COM). STUDY DESIGN: Quasi-randomised clinical trial. SETTING: Tertiary referral centre. MATERIALS AND METHODS: Patients with chronic perforations and mucosal COM undergoing endoscopic transtympanic cartilage myringoplasty were allocated to a control group for whom the perforation edges were preserved (n = 40) and an intervention group for whom the edges were removed (n = 39). Mean operation time, graft success rate, mean scores of graft neovascularisation and epithelialisation, and hearing were compared between the groups at 4 weeks and/or 6 months postoperatively. RESULTS: Graft success rate was 95% (38/40) in the control group and 97% (38/39) in the intervention group at 6 months postoperatively; the difference was not significant. Mean graft neovascularisation scores 4 weeks postoperatively were 2.52 ± 0.59 in the control group and 2.58 ± 0.55 in the intervention group; the difference was not significant. Mean graft epithelisation scores 4 weeks postoperatively were 1.48 ± 0.57 in the control group and 1.68 ± 0.51 in the intervention group; the difference was not significant and remained nonsignificant 6 months postoperatively (2.5 ± 0.55 vs. 2.76 ± 0.36). Audiological outcomes at 6 months did not differ between the groups. CONCLUSION: Endoscopic, transtympanic cartilage underlay myringoplasty with preservation of the perforation margins did not affect graft neovascularisation, epithelialisation or success. Longer-term outcomes and risk of cholesteatoma require further study.

Comparison of long-term outcome of two endoscopic transtympanic myringoplasty without tympanomeatal flap elevating for repairing large chronic perforations.

OBJECTIVE: We compare the long-term efficacy of the cartilage-perichondrium modified over-underlay technique and transtympanic underlay alone technique using endoscopic myringoplasty without tympanomeatal flap elevating for repairing large chronic perforations. MATERIAL AND METHODS: Nine chronic large perforations with mucosal chronic otitis media were recruited and randomly allocated to endoscopic cartilage-perichondrium modified over-underlay myringoplasty (MOUM, n = 55) and endoscopic cartilage-perichondrium transtympanic underlay alone myringoplasty (TUAM, n = 54). The graft success rate, hearing gain, mean operation time and postoperative complications were compared between the groups at 6 and 24 months. RESULTS: In total, 99 patients were finally analysed. The graft success rates 6 months after surgery between MOUM and TUAM groups were not significantly different (100.0% vs 96.0%, p = 0.484). However, the MOUM group had a significantly higher success rate 24 months after surgery than the TUAM group (93.9% vs 76.0%, p = 0.028). In addition, postoperative ABG < 10 dB was 73.5% patients in the MOUM group and 76.0% in the TUAM group, the difference wasn't significant (p = 0.953). CT examination revealed well-pneumatised middle ears 24 months after surgery in both groups, and no middle ear cholesteatoma was observed. CONCLUSION: Endoscopic modified cartilage-perichondrium over-underlay myringoplasty without tympanomeatal flap elevating is reliable and effective for repairing large perforations. It improves the long-term graft success rate compared to the endoscopic cartilage-perichondrium transtympanic underlay alone technique. The risk for iatrogenic cholesteatoma is minimal.

Comparison of Electrocoagulation Tuboplasty and Continued Medical Therapy for Treating Persistent Eustachian Tube Dysfunction With Hypertrophic Mucosa Disease.

OBJECTIVES: The objective of this trial was to compare outcomes of electrocoagulation tuboplasty and continued medical therapy for treating persistent Eustachian tube dysfunction (ETD) with hypertrophic mucosa disease in the Eustachian tube (ET) orifice. STUDY DESIGN: Prospective, case-control trial. MATERIAL AND METHODS: Patients with persistent ETD were recruited and allocated to electrocoagulation tuboplasty and continued medical therapy groups. The ETD questionnaire-7 (ETDQ-7) score and objective parameters were compared between the groups at 6 and 12 months. RESULTS: The proportion of patients with a decrease in ETDQ-7 scores was greater in the electrocoagulation group than in the medical therapy group at the 6-month follow-up (53.49% and 34.38%, respectively; p = .158), but the difference was not statistically significant. However, at the 12-month follow-up, there was a significantly higher proportion of patients with a decrease in ETDQ-7 scores in the electrocoagulation group (88.37% and 40.63%, respectively; p = .001). Additionally, a significant difference was observed between the groups in terms of the proportion of patients who improved 12 months after the treatment (tympanometry: 72.09% and 9.38%, respectively; p = .001; air-bone gap: 79.07% and 25.00%, respectively; p = .001; tympanic membrane status: 62.79% and 0.00%, respectively). In addition, the proportion of patients with improvements in the ET inflammation score was significantly different between the groups at 6-month (67.44% and 34.38%, respectively; p = .009) and 12-month (93.02% and 34.38%; p = .001) follow-ups. No device- or procedure-related serious adverse events were reported in any patients. CONCLUSIONS: Electrocoagulation Eustachian tuboplasty appears to be a safe and feasible procedure for adult persistent ETD with hypertrophic mucosa disease in the ET orifice, and is superior to continued medical management alone. The improvements in ETDQ-7 and objective parameters persisted for 12 months.

Endoscopic inlay cartilage and perichondrium myringoplasty for repairing large perforations in teenagers.

OBJECTIVE: This study compared the long-term graft success rates and hearing outcomes of overlay-underlay and underly cartilage myringoplasty for repairing large perforations in Teenagers. STUDY DESIGN: prospective, randomized study. SETTING: Tertiary referral center. METHODS: Pediatric patients older than 12 years with chronic perforations were randomly divided into two groups:intervention group (n = 39) and control group (n = 41). The graft success rate, hearing improvement, and complications were compared between the two groups. RESULTS: A total of 80 patients were included in this study. The graft success rate was 100% in the intervention group and 95.1% in the control group at postoperative 3 months, the difference wasn't significant (P = 0.496). Also, the graft success rate was not significantly different between the two groups at 12 months postoperatively (100.0% vs 87.8%, p = 0.073). However, the difference of graft success rate was significant between the two groups at 24 months postoperatively (97.4% vs 75.6%, p = 0.012). CT examination revealed well-pneumatized middle ears 24 months after surgery in both group. However, epithelial pearls near the umbo were seen at 31 months postoperatively in one patient in the observation group. CONCLUSIONS: Compared to the endoscopic cartilage with perichondrium composite graft underlay technique, endoscopic perichondrial graft overlay and cartilage underlay had a better long-term graft success rate and lower rate of long-term re-perforation in teenagers. However, the graft technique had no effect on hearing outcome.

Topical Application of bFGF Alone for the Regeneration of Chronic Tympanic Membrane Perforations: A Preliminary Case Series.

RESULTS: A total of 29 patients consisting 13 in the bFGF alone group and 16 in the myringoplasty group were finally included in the analysis. Of the 13 patients in the bFGF alone group, the perforations were small in 6 and medium in 7; the etiology was secondary to COM in 11 and to trauma in 2. One patient with an unhealed perforation continued bFGF treatment until 6 months, while the others stopped at 3 months. Of the seven medium-sized perforations, none of the five COM perforations closed, while the two traumatic perforations achieved complete closure within 2 and 4 weeks, respectively. The successful closure rate was 28.6% (2/7). Successful closure was achieved in 66.7% (4/6) of the six small perforations with COM, with a mean closure time of 4.75 weeks. Of the 16 patients in the myringoplasty group, all perforations were medium-sized and were secondary to COM in 15 cases and traumatic in 1 case; all achieved complete closure. CONCLUSIONS: bFGF alone facilitated the repair of chronic traumatic perforations and small perforations with COM, but not medium-sized perforations with COM. These observations indicated that the regenerative conditions of traumatic perforations are better than those of COM perforations when using bFGF alone, and that graft materials could play a critical role in the regeneration of larger-sized chronic perforations with COM.

The feasibility of intranasal endoscopic microwave ablation on the removal of nasolabial cyst: Preliminary case series.

OBJECTIVE: The aim of this study was to investigate the clinical effect of the removal of nasolabial cyst via intranasal endoscopic microwave ablation (MWA). METHODS AND MATERIALS: The patients with nasolabial cyst were ablated through intranasal endoscopic MWA. Postoperative pain intensity was measured via visual analogue scale (VAS), post-operative complications were recorded. RESULTS: Of the 31 patients with unilateral nasolabial cyst, the main complaint was a gradually increasing mass in the nasal alar and upper lip, other complaint included nasal obstruction (11/31,35.5%), localized pain (21,67.7%), and erythema (13/31,41.9%). All 31 patients were successfully treated with the intranasal endoscopic ablation technique in outpatient. The mean ablation duration was 5.86 ± 0.71 min. The mean VAS pain score was 2.36 ± 1.08 on postoperative. None of infection occurred. All the patients complained of mild numbness in the upper lip with an average last duration of 28.5 ± 7.9 h in patients. In addition, 4 (12.9%) patients had facial/perinasal swelling, acid bilge of maxillary teeth in 7(22.6%), and toothache in one (3.2%). The patients were followed up for 12 months without recurrence and oronasal fistula. The nasolabial cyst had integrated into a part of the nasal cavity. CONCLUSIONS: The intranasal endoscopic MWA is feasible and alternative to conventional transoral sublabial approach for removal of the nasolabial cysts in outpatient.

Is no de-squamatization of the TM reliable for cartilage over-underlay myringoplasty without external auditory canal packing?

OBJECTIVE: We evaluated the graft and hearing outcomes of patients with chronic perforations treated via the cartilage-perichondrium over-underlay technique without de-squamatization of the TM and external auditory canal (EAC) packing. MATERIALS AND METHODS: Thirty-nine patients with chronic perforations and residual tympanic membranes around the perforation margins were treated using the cartilage-perichondrium over-underlay technique without de-squamatization of the TM and EAC packing. Patients were followed-up for 6 months. RESULTS: For all 39 patients with unilateral perforations, the graft success rate was 100% (39/39) at 6 months after surgery. The mean air-bone gap significantly (P < 0.05) improved from 13.41 ± 8.34 dB preoperatively to 7.45 ± 3.81 dB postoperatively in patients with small and medium perforations; the mean air-bone gap significantly improved from 20.57 ± 9.41 dB preoperatively to 9.84 ± 2.41 dB postoperatively in patients with large perforations. The lateral perichondrium gradually became necrotic and crust at postoperative 2-3 months and migrated into the EAC in all patients. CONCLUSIONS: The cartilage-perichondrium over-underlay myringoplasty without de-squamatization of the TM and EAC packing is feasible, affording a high graft success rate and good hearing improvement. The lateral perichondrium may gradually become necrotic and crusted, and migrate along the EAC over time.