Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinoma.

The current study tested the expression and potential functions of Gαi1 in nasopharyngeal carcinoma (NPC). The Cancer Genome Atlas (TCGA) database results demonstrate that Gαi1 transcripts' number in NPC tissues is significantly higher than that in the normal nasal epithelial tissues. Its overexpression correlates with poor survival in certain NPC patients. Moreover, Gαi1 is significantly upregulated in NPC tissues of local primary patients and in different primary human NPC cells. Whereas its expression is relatively low in cancer-surrounding normal tissues and in primary nasal epithelial cells. Genetic silencing (via shRNA strategy) or knockout (via CRISPR-sgRNA method) of Gαi1 substantially suppressed viability, proliferation, cell cycle progression, and migration in primary NPC cells, causing significant caspase-apoptosis activation. Contrarily, ectopic Gαi1 expression exerted pro-tumorigenic activity and strengthened cell proliferation and migration in primary NPC cells. Gαi1 is important for Akt-mTOR activation in NPC cells. Akt-S6K phosphorylation was downregulated after Gαi1 shRNA or KO in primary NPC cells, but strengthened following Gαi1 overexpression. In Gαi1-silenced primary NPC cells, a S473D constitutively-active mutant Akt1 (caAkt1) restored Akt-S6K phosphorylation and ameliorated Gαi1 shRNA-induced proliferation inhibition, migration reduction and apoptosis. Bioinformatics analyses proposed zinc finger protein 384 (ZNF384) as a potential transcription factor of Gαi1. In primary NPC cells, ZNF384 shRNA or knockout (via CRISPR-sgRNA method) decreased Gαi1 mRNA and protein expression, whereas ZNF384 overexpression upregulated it. Importantly, there was an increased binding between ZNF384 protein and the Gαi1 promoter in human NPC tissues and different NPC cells. In vivo studies showed that intratumoral injection of Gαi1-shRNA-expressing adeno-associated virus (AAV) impeded subcutaneous NPC xenograft growth in nude mice. Gαi1 downregulation, Akt-mTOR inactivation, and apoptosis induction were detected in Gαi1-silenced NPC xenograft tissues. Gαi1 KO also effectively inhibited the growth of NPC xenografts in nude mice. Together, overexpressed Gαi1 exerts pro-tumorigenic activity in NPC possibly by promoting Akt-mTOR activation.

[λ approach for the repairment of large skin defects after resection of preauricular fistula with cellulitis in children].

Objective:To explore the feasibility and advantages of λ approach for the repairment of large skin defects after resection of preauricular fistula with cellulitis in children. Methods:The clinical data of patients with preauricular fistula with cellulitis treated by λ approach from January 2016 to January 2021 were analyzed retrospectively. Results:After follow-up for 10-18 months, the primary healing rate of incision was 97.8%, and the survival rate of λ flap was 100%. Conclusion:λ approach is a safe, effective and cosmetic method. It can be used to repair the large skin defects after resection of preauricular fistula with cellulitis in children.

[Hyoid body morphology of thyroglossal duct cyst: a comparative study based on imaging].

Objective:To provide reference for preoperative diagnosis and treatment of thyroglossal duct cyst by studying the morphological changes of hyoid body. Methods:The CT data（midsagittal image） of congenital thyroglossal duct cyst（TGDC group） diagnosed by pathology and the control group（C group） were collected from January 2016 to October 2021. The differences of hyoid body height（HBH）, hyoid body width（HBW）, hyoid bone thickness（HBT）, HBW/HBH, HBT/HBH between the two groups were compared. HBH, HBW and HBT were analyzed by t-test; The HBW/HBH and HBT/HBH were analyzed by Mann-Whitney U test. Results:Twenty-nine cases were included in the TGDC group and 58 in the C group. The HBH in the TGDC group was（8.93 ±0.22） mm and that in the C group was（8.94±0.12） mm, there was no significant difference between the two groups（P>0.05）. The HBW in the TGDC group and the C group were（5.09±0.21） mm and（4.48±0.11） mm, and the HBT were（3.84±0.12） mm and（3.13±0.08） mm, respectively, the difference between the two groups was statistically significant（P<0.05）. The average rank sum of HBW/HBH in the TGDC group and the C group was 53.95 and 39.03, respectively, and the average rank sum of HBT/HBH was 59.90 and 36.05, respectively, the difference between the two groups was statistically significant（P<0.05）. Conclusion:The morphological changes of hyoid body of thyroglossal duct cyst may be helpful for preoperative diagnosis, and it also suggests that hyoid body resection may reduce the possibility of postoperative recurrence.

Identification of Gαi3 as a novel molecular therapeutic target of cervical cancer.

Here we studied expression and potential functions of Gαi3 in cervical cancer. The bioinformatics analysis together with the results from local patients' tissues revealed that Gαi3 expression was remarkably elevated in human cervical cancer tissues and different cervical cancer cells, and was associated with poor overall survival and poor disease-specific survival of patients. Gαi3 depletion resulted in profound anti-cervical cancer activity. In primary or immortalized cervical cancer cells, Gαi3 shRNA or CRISPR/Cas9-caused Gαi3 knockout/KO largely hindered cell proliferation and migration, and provoked apoptosis. On the contrast, ectopic Gαi3 overexpression further enhanced cervical cancer proliferation and migration. Akt-mTOR activation in primary cervical cancer cells was significantly reduced after Gαi3 silencing or KO, but was augmented following Gαi3 overexpression. Further studies revealed that the transcription factor GATA4 binding to Gαi3 promoter region was significantly enhanced in cervical cancer tissues and cells. Gαi3 expression was decreased by GATA4 shRNA, but upregulated following GATA4 overexpression. In vivo, the growth of cervical cancer xenografts was robustly suppressed after Gαi3 silencing or KO. Gαi3 depletion and Akt-mTOR inactivation were detected in Gαi3-silenced/-KO cervical cancer xenograft tissues. Together, upregulated Gαi3 is a valuable oncotarget of cervical cancer.

The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma.

It is urgent to identify and validate biomarkers for early diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC). Recent studies have proposed p38 gamma (p38γ) as a cyclin-dependent kinase (CDK)-like kinase that phosphorylates retinoblastoma (Rb) to promote cyclins expression and tumorigenesis. Here the Gene Expression Profiling Interactive Analysis (GEPIA) database and results from the local NPC tissues demonstrate that p38γ is significantly upregulated in NPC tissues, correlating with poor overall survival. Furthermore, p38γ mRNA and protein expression is elevated in established NPC cell lines (CNE-1 HONE-1 and CNE-2) and primary human NPC cells, but low expression detected in human nasal epithelial cells. In established and primary NPC cells, p38γ depletion, using the shRNA strategy or the CRISPR/Cas9 gene-editing method, largely inhibited cell growth, proliferation and migration, and induced significant apoptosis activation. Contrarily, ectopic p38γ overexpression exerted opposite activity and promoted NPC cell proliferation and migration. Retinoblastoma (Rb) phosphorylation and cyclin E1/A expression were decreased in NPC cells with p38γ silencing or knockout, but increased after p38γ overexpression. Moreover, mitochondrial subcellular p38γ localization was detected in NPC cells. Significantly, p38γ depletion disrupted mitochondrial functions, causing mitochondrial depolarization, reactive oxygen species production, oxidative injury and ATP depletion in NPC cells. In vivo, intratumoral injection of adeno-associated virus-packed p38γ shRNA potently inhibited primary human NPC xenograft growth in nude mice. In p38γ shRNA virus-injected NPC xenograft tissues, p38γ expression, Rb phosphorylation, cyclin E1/A expression and ATP levels were dramatically decreased. Taken together, we conclude that p38γ overexpression is required for NPC cell growth, acting as a promising therapeutic target of NPC.

[Eigenvalue analysis of wideband acoustic immittance in secretory otitis media in children of different ages].

Objective:The characteristic values of broadband acoustic immittance of children of different ages during secretory otitis media were collected resonance frequency and absorption rate of middle ear in children of different ages were compared. Methods:Eighty-two children with secretory otitis media were selected for the broadband acoustic immittance test, including 62 cases （83 ears） in the young effusion group（[3.5±0.7]months）, and 20 cases （40 ears） in the older effusion group（[4.0±0.6]years old）. 82 normal children were selected for broadband acoustic immittance test in the same environment, including 62 cases （124 ears） in the younger normal group and 20 cases （40 ears） in the older normal group. The resonance frequency and absorptivity of different age groups under broadband peak pressure were compared, and the frequency absorptivity curve was drawn for analysis. Results:The resonance frequencies of older normal group and younger normal group, older effusion group and older normal group, younger effusion group and younger normal group, older effusion group and younger effusion group were statistically significant（P<0.001）. Analysis of sound energy absorption rate at different ages. There was significant difference in sound energy absorption rate between older normal group and younger normal group at 226-1155 / 4757-8000 Hz（P<0.001）. The difference of full frequency sound energy absorption rate between the older effusion group and the older normal group was statistically significant（P<0.001）, among which the difference of 866-1542 / 2520-4362 Hz absorption rate was the largest. The difference of full frequency sound energy absorption rate between young effusion group and young normal group was statistically significant（P<0.001）, and the difference of 1091-2245 / 3776-5494 Hz absorption rate was the largest. Conclusion:Middle ear effusion in children of different ages has different performance under broadband acoustic immittance peak pressure, and has its own characteristic acoustic energy absorption frequency band. This study provides a reference basis for the analysis of the characteristics of middle ear sound transmission in children with secretory otitis media in the future.

[Common clinical causes and audiological manifestations of unilateral hearing loss in children].

Objective:To analyze the common clinical causes and audiological manifestations of unilateral hearing loss in children, and to provide a basis for early prevention and intervention. Method:A retrospective analysis of 20 cases of children diagnosed with unilateral hearing loss was conducted. The medical history was collected, followed by audiological and imaging examinations. Result:The audiological performance of 20 children with unilateral hearing loss: 1 case of conductive deafness, whose hearing curve was flat and showed moderate hearing loss. There were 19 cases of sensorineural deafness, of which 1 case was moderate deafness, 16 cases were severe deafness, and 2 cases were extremely severe deafness. The imaging results showed that there were 1 case with transverse fracture of the temporal bone, 1 case with congenital cholesteatoma, 9 cases with dysplasia of the cochlear nerve, and 4 cases with malformation of the inner ear. The history of the two children was collected and there were clear congenital cytomegalovirus infection and mumps virus infection. The causes of the remaining 3 cases were unknown. Conclusion:Unilateral hearing loss in children is a common clinical diseasewith complex and diverse causes. Carefully analysis should be made to find out the causes and symptomatic treatment to provide a basis for early prevention and intervention of children's hearing.

[Three cases of eosinophilichyperplastic lymphogranuloma in children's parotid area].

From March 2009 to October 2009, three pediatric patients with parotid tumor were cured. Preoperative physical examination showed regional swelling in parotid area, the surface skin was in moderate reddish purple, the border was vague, and the swelling was inactive. The patients' IgE were significantly increased. B ultrasound examination demonstrated the focus was an isoecho with ringlike dark band around, which was concluded as bull's-eye sign. Magnetic resonance imaging (MRI) examination indicated a cystic mass between the skin and parotid. Preoperative diagnosis was eosinophilichyperplastic lymphogranuloma (Kimura's disease) and the granuloma was excised by operation. Pathological examination revealed the capillary vessel hyperplasia in local tissue with a plenty of eosinophils and lymphocytes infiltrating. The disease was confirmed. Although the disease is rare, the diagnosis still could be made by preoperative physical examination, laboratory and imaging examinations.