Endoscopic Dyeing and Plasma Coblation-Assisted Open Neck Surgery for Pyriform Fossa Branchial Apparatus Anomalies in Adults.

Objective: Pyriform fossa (PF) branchial apparatus anomalies (PFBAA) are rare congenital third or fourth branchial apparatus anomalies (TBAA or FBAA). This article summarizes our paradigm in managing this condition by combining endoscopic procedures and open neck surgery. Methods: A retrospective review was undertaken concerning PFBAA cases treated at our tertiary medical institution between July 2020 and November 2023. Data were collected from case records. Three sequential steps were implemented: (1) direct laryngoscopy to identify internal orifice (IO), with injection of methylene blue into it; (2) open neck surgery to resect all inflammatory tissues, focusing on the ligation of the sinus tract out of PF; and (3) plasma coblation of IO mucosa. Results: In total, 7 cases (4 men and 3 women) were included (28-67 years old, median age 53). Presenting symptoms were various, with 6 lesions on the left and 1 on the right side. Preoperative (PO) fiberoptic laryngoscopy identified IO in 6 patients, while PO barium esophageal study identified outflow from PF in 4 patients. A preliminary diagnosis of PFBAA could be established in all cases (2 TBAA and 5 FBAA cases). Direct laryngoscopy after general anesthesia identified IO in all cases (2 on the base of PF and 5 on the apex of PF). All the surgical procedures were successful, with uneventful recovery in all the patients. No postoperative complications were observed. All the patients resumed oral fluid intake after confirmation of no pharyngeal fistula by barium esophageal study on the seventh postoperative day. The duration of follow-up was between 6 and 40 months (with a median duration of 27 months). No recurrence was observed. Conclusion: Open neck surgery, assisted by endoscopic dyeing of sinus tracts and plasma coblation of IO mucosa, is a suitable treatment for PFBAA in adults. This paradigm is effective and safe for senior surgeons.

Application of 18ß-glycyrrhetinic acid in the structural modification of natural products: a review.

18ß-Glycyrrhetinic acid (GA) is an oleane-type pentacyclic triterpene saponin obtained from glycyrrhizic acid by removing 2 glucuronic acid groups. GA and its analogues are active substances of glycyrrhiza aicd, with similar structure and important pharmacological effects such as anti-inflammatory, anti-diabetes, anti-tumor and anti-fibrosis. Although GA combined compounds are in the clinical trial stages, its application potential is severely restricted by its low bioavailability, water solubility and membrane permeability. In this article, synthetic methods and structure-activity relationships (SARs) of GA derivatives from 2018 to present are reviewed based on pharmacological activity. It is hoped that this review can provide reference for the future development of potential GA preclinical candidate compounds, and furnish ideas for the development of pentacyclic triterpenoid lead compounds.

Carbon nanoparticles beneficial for prophylactic central compartment lymph node dissection in cN0 papillary thyroid carcinoma.

Objective: This study explored prophylactic central compartment lymph node dissection (pCCLND) for patients with cN0 papillary thyroid carcinoma (PTC) and the effect of carbon nanoparticles (CNP) on surgical outcomes. Methods: This retrospective study reviewed PTC cases treated at our tertiary medical institution between January 2019 and December 2022. Only patients with indications for total thyroidectomy and cN0 disease were included. CNP has been associated with a higher number of harvested lymph nodes and a lower rate of accidental parathyroid gland (PTG) removal. Patients who used CNP in this study were classified as group 1, while those who denied its use were classified as group 2. Results: In total, 116 cases were included, with 80 patients in group 1 and 36 in group 2. Most patients were in stage T1, with 68 (85.0 %) patients in group 1 and 31 (86.1 %) in group 2. Postoperative hoarseness occurred in 3 (3.8 %) patients in group 1 and 1 (2.8 %) in group 2, which recovered within two months. In group 2, 250 nodes were harvested, 72 (28.8 %) of which were metastatic; in group 1, 889 nodes were harvested, 316 (35.5 %) of which were metastatic; the difference regarding the rates of metastatic lymph nodes between the 2 groups was statistically significant (P = 0.047). Differences in postoperative blood calcium and parathyroid hormone levels between the two groups were statistically significant (P = 0.035 and P = 0.034, respectively). There were symptoms of hypocalcemia in 6 (16.7 %) patients in group 2 but in only 2 (2.5 %) in group 1, all of which recovered within three months; the difference was statistically significant (p = 0.017). Conclusion: pCCLND is worth undertaking for cN0 PTC. CNP is beneficial for achieving more thorough dissection and reducing temporary hypoparathyroidism.

Intracapsular Enucleation of Brachial Plexus Schwannoma With Intraoperative Neuromonitoring: A Case Series Study and a Review of Literature.

OBJECTIVE: Brachial plexus schwannoma (BPS) is a rare clinical entity that poses a significant challenge for head and neck surgeons due to its neuroanatomical complexity and potential severe complications, such as major motor or sensory neurological deficits or pain of the corresponding upper extremity. This article summarizes our experience in its diagnosis and intracapsular enucleation with intraoperative neuromonitoring (INM). METHODS: A retrospective review of BPS cases treated at our tertiary medical institution was conducted between April 2020 and May 2023. The clinical and demographic data were retrieved from case notes. RESULTS: Totally, 3 cases were included. All 3 patients were male, aged 43 to 54 years (median age = 52). The presenting symptom was a palpable supraclavicular mass in all these cases (2 on the left side and 1 on the right side). Neuromonitoring was performed with a 4-channel nerve integrity monitor, with the electrodes placed in the upper arm and forearm muscles, as demonstrated in the literature. After exposing the mass and identifying its origin from the brachial plexus, a unipolar stimulating probe was used to stimulate the tumor surface or the nerves with a 1.0-mA current, and a longitudinal incision into the tumor capsule was made along a carefully mapped line with no INM response. Then the mass was carefully exposed and meticulously dissected from its capsule to achieve an intact enucleation. Immediate postoperative neurological deficit was documented in Case 1 as a mild grasping weakness. The recovery of the other 2 patients was uneventful. The follow-up duration was 7 to 38 months (median = 8 months). The minor motor deficit of Case 1 recovered completely 1 month after surgery. No recurrence of BPS was observed. CONCLUSIONS: Intracapsular enucleation with INM could result in complete removal of BPS and minimal postoperative neurological deficit, whose recovery was quick and satisfactory.

Diagnosis and Open Surgical Management of Laimer's Diverticulum: Case Series and Review of the Literature.

Objectives: Laimer's diverticulum (LD) is a very rare clinical entity originating between the cricopharyngeus muscle (CPM) and circular muscular fibers of the esophagus. Its diagnosis and management remain to be elucidated. This article summarizes our experience in its diagnosis and open surgical management.Methods: A retrospective review of LD cases treated at our tertiary medical institution was conducted between July 2018 and May 2023. The clinical and demographic data were retrieved from case notes.Results: Three cases were included in this review. There were 2 male patients and 1 female patient. The average and median ages were 47.3 and 54 years, respectively. Presenting symptoms included hoarseness, pharyngeal foreign body sensation, and neck mass. All 3 diverticula were on the left side, with the first 2 cases discovered accidentally on gastric endoscopic or cervical MRI examinations. After evaluating esophageal swallowing with barium sulfate or urografin contrast media, all the patients consented to undergo an open surgical procedure. During surgical exploration, the diverticula were found to be on the posterior part of the cervical esophagus, below CPM, and away from the recurrent laryngeal nerve, and only then, could the diagnosis of LD be established. Then, diverticulectomy and manual suturing of the esophagus was performed. Recovery of all 3 patients was uneventful. Nasogastric tube feeding lasted 7 to 12 days until esophageal examinations demonstrated no leak, and then, oral liquid feeding resumed. The median duration of follow-up was 50 months. No recurrence of symptoms or diverticulum was observed, and the swallowing function of all 3 patients was excellent.Conclusions: An open surgical approach is not only important for the diagnosis of LD, but can also be utilized as a safe and effective treatment.

Synthesis and antimicrobial activity evaluation of pyrazole derivatives containing the imidazo[2,1-b][1,3,4]thiadiazole moiety.

Four series of novel pyrazole derivatives (compounds 17a-m, 18a-m, 19a-g, and 20a-g) were synthesized, and their antibacterial and antifungal activities were evaluated. Most of the target compounds (17a-m, 18k-m, and 19b-g) showed strong antifungal activity and high selectivity relative to both Gram-positive and Gram-negative bacteria. Among them, compounds 17l (minimum inhibitory concentration [MIC] = 0.25 µg/mL) and 17m (MIC = 0.25 µg/mL) showed the strongest antifungal activity, being 2- and 4-fold more active than the positive controls gatifloxacin and fluconazole, respectively. In particular, compound 17l showed little cytotoxicity against human LO2 cells and did not exhibit hemolysis at ultrahigh concentrations, as did the positive control compounds gatifloxacin and fluconazole. These results indicate that these compounds are valuable for further development as antifungal agents.

Synthesis and Antibacterial Activity Evaluation of Imidazole Derivatives Containing 6-Methylpyridine Moiety.

A series of 2-cyclopropyl-5-(5-(6-methylpyridin-2-yl)-2-substituted-1H-imidazol-4-yl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazoles (15a-t and 16a-f) were synthesized and their antibacterial activities were evaluated. More than half of the compounds showed moderate or strong antibacterial activity. Among them, compounds 15t (MIC=1-2 µg/mL) and 16d (MIC=0.5 µg/mL) showed the strongest antibacterial activities. Notably, compound 16d did not exhibit cytotoxicity in HepG2 cells and did not show hemolysis like the positive control compound Gatifloxacin. The results suggest that compound 16d should be further investigated as a candidate antibacterial agent.

Efficacy of Larynx Preservation Surgery and Multimodal Adjuvant Therapy for Hypopharyngeal Cancer: A Case Series Study.

Background: Larynx preservation surgery (LPS) combined with multimodal adjuvant therapy (MAT) is re-emerging as treatment option for hypopharyngeal cancer (HPC). This study aims to explore the survival and functional outcome of this combined approach. Methods: This is a retrospective cohort study. Selected patients with primary HPC treated by LPS and MAT at two large Beijing medical centers between 2005 and 2019 were included. In addition to LPS, patients received one or more of the following treatments: preoperative induction chemotherapy, postoperative intensity-modulated radiotherapy, chemotherapy, or targeted therapy. Results: In total, 64 patients were included (62 were men, and median age was 57.5 years). The disease in most patients was in stage III (28.1%) or IV (56.3%), or in stage T2 (34.4%) or T3 (45.3%), based on the TNM scale. Across all patients, the rate of overall survival (OS) was 60.7% at 3 yr and 47.3% at 5 yr. OS was significantly higher for patients with stage I or II disease than for those with stage III or IV disease (HR 8.64, 95% CI 3.69-20.2, log-rank P = .010). Decannulation was successful in 55 patients (85.9%), and swallowing function was satisfactory (stage 0-III, on Functional Outcome Swallowing Scale) for 50 (78.1%). Median Voice Handicap Index-10 score on voice performance was 19 (range 4-40), and median Functional Assessment of Cancer Therapy-General Questionnaire score for QoL was 75 (range 16-105). Conclusions: LPS and MAT can provide satisfactory oncologic control and good functional outcomes for selected patients with HPC, especially those with stage I or II disease.

Delayed oral feeding reduces pharyngocutaneous fistula formation after open surgical treatment of primary hypopharyngeal cancer: A case-control study.

OBJECTIVES: Pharyngocutaneous fistula (PCF) formation following open surgical treatment of hypopharyngeal cancer (HPC) is a common and troublesome complication. To date, the postoperative protocol of restarting oral intake is not clear, and vast discrepancies exist in the literature and among institutions. This study aimed to explore the impact of a postoperative protocol of restarting oral intake on PCF formation after open surgical treatment of primary HPC, and its impact on overall survival (OS) and swallowing function based on the functional outcome swallowing scale (FOSS). MATERIALS AND METHODS: This was a prospective observational study of 42 patients who received open surgical treatment for primary HPC at Beijing Friendship Hospital between April 2019 and August 2021. This cohort included two groups: patients who restarted oral intake on the 10th postoperative day (Group 1), and those who started on the 20th (Group 2). The Chi-square test and Fisher's exact chi-squared test were used for comparing qualitative data among the groups. RESULTS: Group 1 (n = 27) and Group 2 (n = 15) were comparable in clinical characteristics. PCF occurred in 7 (25.9%) patients in Group 1, while none occurred in Group 2 (P = 0.038). The 2-year OS of all 42 patients was 75.6%; 65.8% and 93.3% for Groups 1 and 2, respectively (P = 0.07). The swallowing function was satisfactory (FOSS Grades 0-III) for 19 (70.4%) patients in Group 1 and 15 (100%) patients in Group 2 (P = 0.035). Laryngeal preservation was achieved in 25 (59.5%) patients, while decannulation was successful in 22 (88.0%) patients. CONCLUSIONS: Delayed oral feeding significantly reduces PCF after open surgical treatment of primary HPC, and improves the swallowing function outcome without jeopardizing the OS.

Intracapsular Enucleation of Cervical Sympathetic Chain Schwannoma.

OBJECTIVES: Schwannoma arising from cervical sympathetic chain (CSC) is a rare clinical entity. CSC is hard to preserve in CSC schwannoma (CSCS) surgeries, resulting in Horner's syndrome (HS) and first bite syndrome (FBS). This article aims to explore our experience in successful preservation of CSC in CSCS surgeries. METHODS: This is a retrospective review of CSCS cases treated at our tertiary medical institution between Apr 2018 and March 2022. Only cases with successful intraoperative preservation of CSC were included. RESULTS: In total, 3 cases were included. There were 2 male patients and 1 female patient. Their age was between 38 years old and 66 years old (average and median age was 52 and 51 years old, respectively). Presenting symptom was neck mass for all them, 2 of which were on the left side, while 1 was on the right. Intracapsular enucleation of the CSCS was attempted and achieved in all 3 cases. Hemorrhage from the inner surface of capsules was diffuse and heavy. Constant saline irrigation, suction, and bipolar coagulation were needed to achieve hemostasis. Postoperative HS presented between 4 hours and 14 hours after surgery for all 3 patients, which took 1 month to 3 months to recover, whereas FBS did not occur in any patient. Median duration of follow-up was 6 months. No recurrence was observed. CONCLUSIONS: Intracapsular enucleation should be attempted in CSCS surgeries, although hemorrhage might be diffuse and hard to control. When intracapsular enucleation was achieved, postoperative FBS can be avoided, while postoperative HS could occur, but its recovery was satisfactory.

Identification of multiple single-nucleotide variants for clinical evaluation of Helicobacter pylori drug resistance.

Helicobacter pylori infections are threats to public health due to their high infection rate and drug resistance. Identification of single-nucleotide variants (SNVs) in H. pylori is crucial for both diagnosis and therapy. Yet the clinical testing of resistant H. pylori mutants is still facing some challenges, such as the selectivity is not good enough for SNVs in abundant wild-type DNA, the lack of clinical validation and the economical burden on patients. Herein, an X-shaped DNA probe with a toehold initiator was designed, which could specifically hybridize with certain genotype DNA due to the thermodynamically driven reaction. A competitive reaction was developed to amplify the thermodynamic difference between wild-type DNA and SNVs, diminishing the interference of wild-type DNA. By this means, multiple SNVs in H. pylori were successfully identified and two SNVs related to clarithromycin resistance are chosen as model targets. A paper strip was fabricated for visual, fast screening of SNVs. Furthermore, the approach was validated using clinical samples, and a point-of-care (POCT) testing diagnosis was executed on saliva samples, demonstrating its potential for the prevention and cure of H. pylori infections.

Survival and swallowing function outcome impact factors analysis of surgery-oriented comprehensive treatment for hypopharyngeal cancer in a series of 122 patients.

OBJECTIVE: Under current standards of treating highly aggressive hypopharyngeal cancer (HPC), oncological control and functional outcome are still unsatisfactory worldwide. This study explored the surgery-oriented comprehensive treatment approach based on 15 years of practice. METHODS: A retrospective cohort of HPC patients treated by the senior author at Chinese PLA General Hospital between Nov 2005 and Aug 2012 and Capital Medical University Beijing Friendship Hospital between May 2014 and Nov 2019 was studied. Oncological control, swallowing function, and quality of life (QoL) were assessed. RESULTS: In total, 122 patients were included in this study, with 11 (9.0%) cases in the early stage and 111 (91.0%) cases in the advanced stage. Five-year overall survival (OS) and disease-free survival (DFS) were 40.0% and 36.1%, respectively. The swallowing outcome was satisfactory in 90 (73.8%) patients. Tracheostomy-free survival was achieved in 55 (45.1%) patients. Multivariate cox regression analysis showed that the size of the surgical defect, local-regional recurrence, and distant metastasis were independent impact factors for OS and DFS (P < .05). Multivariate analysis showed that the logistic regression coefficients (standard error) of pharyngo-cutaneous fistula and local-regional recurrence on swallowing function were 1.274 (.532) and 1.283 (.496), respectively (P < .05). In addition, the logistic regression coefficients (standard error) of the clinical stage, local-regional recurrence, decannulation, and feeding tube on QoL were -7.803 (3.593), -7.699 (3.151), 13.853 (3.494), and -20.243 (3.696), respectively (P < .05). CONCLUSIONS: Surgery-oriented comprehensive treatment can give rise to good swallowing function without jeopardizing oncological control. The size of the surgical defect, local-regional recurrence, and distant metastasis were independent factors impacting OS and DFS. Pharyngo-cutaneous fistula and local-regional recurrence were independent factors impacting swallowing function. Clinical stage, local-regional recurrence, decannulation, and feeding tube were independent factors impacting QoL.

Diagnosis and Management of Occult Cervical Tuberculous Lymphadenopathy.

Objective: Some cervical tuberculous lymphadenopathy (CTL) presents no evidence of tuberculosis (TB), even after thorough examination of a fine-needle aspiration (FNA) specimen. After the examination of excisional specimens, when the polymerase chain reaction (PCR) analysis identifies the nucleic acid of Mycobacterium tuberculosis (Mtb) or the culture results are positive, then the diagnosis of CTL is established. We refer to this condition as occult CTL (OCTL). Patient and Methods: The present work is a retrospective review of a consecutive series of OCTL cases that were treated at the Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, between June 2015 and September 2020. When the diagnosis of OCTL was established, the patients received the standard anti-TB chemotherapy. Results: Fourteen cases of OCTL, including 9 female and 5 male patients, aged 24 to 71 years (median age 42 years), were included in the present study. The most commonly observed levels of lymph node involvement were level V and level II. Each level of the involved lymph nodes was removed entirely through en bloc surgical resection. An evaluation of the excisional specimens led to positive PCR results in all 14 cases, with 2 cases presenting positive culture and 3 cases exhibiting positive acid-fast bacilli (AFB) staining. Recovery was uneventful, and the anti-TB chemotherapy was completed in all cases. The median duration of follow-up was 29 months, during which no case of TB relapse was observed. Conclusions: Wide surgical excision is crucial for the diagnosis and management of OCTL, and when used in combination with anti-TB chemotherapy, it results in satisfactory patient outcomes.

Diagnosis and Management of Giant Esophageal Fibrovascular Polyp With Hypopharyngeal Pedicle.

Background: Fibrovascular polyps (FVPs) with hypopharyngeal pedicles (hFVPs) are the rare intraluminal benign tumours of the upper aerodigestive tract, and their accurate diagnosis and optimal management are challenging. Purpose: The present retrospective study attempted to explore the optimal diagnosis and treatment of hFVPs. Research Design: The clinical records of 2 patients with giant, irregularly shaped hFVPs, who underwent several failed surgical procedures after inaccurate diagnosis, were reviewed. Finally, the patients were correctly diagnosed and successfully treated at Capital Medical University Beijing Friendship Hospital in different years, 2018 and 2020. Results: Case 1 was of a 43-year-old woman with 2 months of progressive dysphagia. Gastroenterologists overlooked the origin of her FVP, and decided to sever its narrowest point in the oesophagus through endoscopy. However, upon unsuccessful removal of the mass, a gastrotomy procedure was performed to extract the mass 7 days later. Symptoms recurred 3 months after the treatment, and a fibreoptic laryngoscopy confirmed hFVP in the patient at our department. A transcervical approach was used to sever the hypopharyngeal pedicle, achieve haemostasis and remove the oesophageal tumour. No recurrence was detected during the 2-year follow-up period after the treatment. Case 2 was of a 32-year-old man with dysphagia who had previously undergone transthoracic and transcervical oesophagotomy procedures within a gap of 3 months for the removal of FVP causing dysphagia. The hypopharyngeal pedicle was not diagnosed in the patient. The symptoms of dysphagia recurred 4 years after the treatment, and a fibreoptic laryngoscope confirmed hFVP at our department. The tumour was removed successfully through the transcervical approach. No recurrence was detected during the 6-months follow-up after surgery. Conclusion: In conclusion, the transcervical approach is suitable for achieving haemostasis and removing giant, irregularly shaped hFVPs.

Management of deep neck infections from cervical esophageal perforation caused by foreign body: A case series study.

PURPOSE: Esophageal perforation caused by foreign body is common in Chinese medical institutions, and resultant deep neck infections (DNI) is quite different from typical DNI. The purpose of this article was to share our experience on management of this particular type of DNI. MATERIAL AND METHODS: A retrospective review was conducted on a consecutive sample of such patients at Capital Medical University Beijing Friendship Hospital from 2015 to 2019. RESULTS: In total, 24 cases were recorded. CT scan of the neck and upper thorax was the most useful tool for early diagnosis. Gas formation was not predictive of a worse clinical course. Eleven patients with minor DNI were treated with antibiotics and foreign body removal; while 13 patients with major DNI were treated with neck incision and drainage, ICU observation, and prolonged usage of antibiotics. Outcome was generally good, but major complications, including sepsis and lingual artery rupture, could occur. CONCLUSIONS: Conservative management, focusing on prompt extraction of esophageal foreign body and adequate antibiotic coverage, can lead to good outcome for mild cases; while in addition to these measures, neck incision, cervical and superior mediastinal exploration, and high negative pressure drainage, should be performed for severe cases.

Surgical treatment of fourth branchial apparatus anomalies: a case series study.

BACKGROUND: Fourth branchial apparatus anomalies, are rare clinical entities, and present as complex cysts, sinuses and fistulae in the neck that can be difficult to manage. METHODS: This is a retrospective review of a series of consecutive patients with fourth branchial apparatus anomalies treated at Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, from Apr 2014 to Nov 2019. RESULTS: Ten patients with fourth branchial apparatus anomalies were identified, including 8 patients with fourth branchial fistula, and 2 patients with fourth branchial pouch sinus. There were 6 female patients and 4 male patients. Their age was from 6 years old to 39 years old (average age 20.4 years old, median age was 21 years old). All 8 fistulae were on the left side, while 2 pouch sinuses were both on the right side. Pre-operative examination with fiberoptic laryngoscope, barium swallow X-ray, CT or MRI identified internal orifice at pyriform fossa apex in 8 (80%) patients. All patients underwent challenging surgical resection by the senior author. Intra-operative direct laryngoscope confirmed or identified internal orifice in 9 (90%) patients. The tracts were all followed to the vicinity of inferior cornu of the thyroid cartilage and the cricothyroid space. Complete resection of cervical lesions and their attachment to hypopharynx were achieved in 9 cases. No complication occurred. One recurrence was detected, in the only patient whose internal orifice could not be located pre- or intra-operatively, and the hypopharyngeal attachment could not be removed. CONCLUSIONS: Direct laryngoscopy under general anesthesia is a reliable method of diagnosis for the fourth branchial apparatus anomalies. Complete surgical removal of fourth branchial apparatus anomalies, including their hypopharyngeal attachment, is the treatment of choice, and the key to prevent recurrence.

Design and application of submental island flap to reconstruct non-circumferential defect after hypopharyngeal carcinoma resection: a prospective study of 27 cases.

BACKGROUND: This study investigated the effects of reconstruction of hypopharyngeal non-circumferential defects with a submental island flap after ablation of hypopharyngeal carcinoma. OBJECTIVES: The purpose of our study was to identify advantages and limitations of the submental flap for reconstruction of non-circumferential hypopharyngeal defects. METHODS: A total of 27 patients who had stage II-IV hypopharyngeal cancer and underwent pharyngeal reconstruction with a submental flap by the senior author in both Department of Otolaryngology Head Neck Surgery, Chinese PLA General Hospital and Department of Otolaryngology Head Neck Surgery, Beijing Friendship Hospital, Capital Medical University. RESULTS: 96.3% (26/27) cases of submental island flap survived. There were two pharyngocutaneous fistulas, one recovered spontaneously, and the other was associated with flap necrosis, underwent neck debridement and flap removal. All except for one patient had decannulation of their nasogastric tube 2 weeks postoperatively. There was no evidence of a stricture or stenosis of the laryngopharynx, nor any sign of aspiration, except for one with esophageal inlet stricture caused by radiotherapy. There were two cases of obvious paraesthesia pharynges due to beard growth at the submental flap after reconstruction. 63.0% (17/27) patients are alive and 37% (10/27) have died of disease. The 3-year survival rate is 56.3% and the 5-year survival rate is 50.0%. CONCLUSION: The submental flap reconstruction for moderately sized non-circumferential hypopharyngeal defects is a recommended treatment option.

Familial nonsyndromic hearing loss with incomplete partition type II caused by novel DSPP gene mutations.

BACKGROUND: Familial nonsyndromic hearing loss (NSHL) with incomplete partition type II (IP-II) is a very rare condition. AIMS/OBJECTIVES: To determine the audiological feature, inheritance patterns and genetic etiology of familial NSHL with IP-II in a Chinese family with eight family members. MATERIAL AND METHODS: Clinical data were collected from all eight family members, selected deafness genes were sequenced in proband and whole genome sequencing of seven family members was performed. RESULTS: The proband were a pair of male nonidentical twins (III:1, III:2). Three patients in this family, including the twins and their father (II:1), were diagnosed with bilateral NSHL with IP-II, and no mutation was found in the genes of SLC26A4, GJB2, GJB3, mitochondrial 12S rRNA, and MITF. Whole genome sequencing data indicated de novo mutations of the gene DSPP, c.3085A > G and c.3087C > T, which resulted in p.N1029D and co-segregated with deafness phenotype, were the underlying genetic etiology. CONCLUSION AND SIGNIFICANCE: Familial NSHL with IP-II is extremely rare. In this family, de novo DSPP gene mutations, were considered to be the most probable genetic etiology. And this is the first report to reveal DSPP gene mutations leading to familial NSHL with IP-II.

Identification and efficacy of glycine, serine and threonine metabolism in potentiating kanamycin-mediated killing of Edwardsiella piscicida.

We previously showed that glucose potentiated kanamycin to kill multidrug-resistant Edwardsiella piscicida through activation of the TCA cycle. However, whether other regulatory mechanism is involved requires further investigation. By quantitative proteomics technology, iTRAQ, we systematically mapped the altered proteins in the presence of glucose and identified 94 differentially expressed proteins. The analysis of the altered proteins by pathways, amino acid biosynthesis and metabolism were enriched. And the most significantly altered eight amino acids tyrosine, phenylalanine, valine, leucine, isoleucine, glycine, serine and threonine were investigated for their potentiation of kanamycin to kill EIB202, where glycine, serine and threonine showed the strongest efficacy than the others. The combinations of glycine and serine or glucose with glycine, serine or threonine had the best effects. Moreover, pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and succinate dehydrogenase activities were increased as well as the proton motive force (PMF) and intracellular kanamycin. Finally, inhibitors that disrupt PMF production abolished the potentiation. These results shed light on the mechanism of how glucose promoting the amino acids biosynthesis and metabolism to potentiate kanamycin to kill antibiotic-resistant bacteria. More importantly, our results suggested that adjusting amino acid biosynthesis and metabolism might be a strategy to become phenotypic resistance to antibiotics in bacteria. SIGNIFICANCE: Tackling antibiotic resistance is an emerging issue in current years. Despite the efforts made toward developing new antibiotics, the progress is still lagged behind expectation. Novel strategies are required. The use of metabolite to revert antibiotic resistant is highly appreciated in recent years due to the less toxicity, more economic and high efficacy. As a continued study of our previous report on glucose potentiating kanamycin to kill antibiotic-resistant bacteria. The current study further expands the previous discovery on the mechanism of how glucose potentiate this effect. This result provides more basis on the action of glucose in reverting antibiotic resistance. And more importantly, we may derive more metabolites other than glucose to manage antibiotic resistance.

Alanine Enhances Aminoglycosides-Induced ROS Production as Revealed by Proteomic Analysis.

Metabolite-enabled killing of antibiotic-resistant pathogens by antibiotics is an attractive strategy to manage antibiotic resistance. Our previous study demonstrated that alanine or/and glucose increased the killing efficacy of kanamycin on antibiotic-resistant bacteria, whose action is through up-regulating TCA cycle, increasing proton motive force and enhancing antibiotic uptake. Despite the fact that alanine altered several metabolic pathways, other mechanisms could be potentially involved in alanine-mediated kanamycin killing of bacteria which remains to be explored. In the present study, we adopted proteomic approach to analyze the proteome changes induced by exogenous alanine. Our results revealed that the expression of three outer membrane proteins was altered and the deletion of nagE and fadL decreased the intracellular kanamycin concentration, implying their possible roles in mediating kanamycin transport. More importantly, the integrated analysis of proteomic and metabolomic data pointed out that alanine metabolism could connect to riboflavin metabolism that provides the source for reactive oxygen species (ROS) production. Functional studies confirmed that alanine treatment together with kanamycin could promote ROS production that in turn potentiates the killing of antibiotic-resistant bacteria. Further investigation showed that alanine repressed the transcription of antioxidant-encoding genes, and alanine metabolism to riboflavin metabolism connected with riboflavin metabolism through TCA cycle, glucogenesis pathway and pentose phosphate pathway. Our results suggest a novel mechanism by which alanine facilitates kanamycin killing of antibiotic-resistant bacteria via promoting ROS production.