Design, Synthesis, and Biological Evaluation of Marine Lissodendrins B Analogues as Modulators of ABCB1-Mediated Multidrug Resistance.

Multidrug resistance (MDR) caused by ATP-Binding Cassette Subfamily B Member 1 (ABCB1, P-glycoprotein, P-gp) is a major barrier for the success of chemotherapy in clinics. In this study, we designed and synthesized a total of 19 Lissodendrins B analogues and tested their ABCB1-mediated MDR reversal activity in doxorubicin (DOX)-resistant K562/ADR and MCF-7/ADR cells. Among all derivatives, compounds D1, D2, and D4 with a dimethoxy-substituted tetrahydroisoquinoline fragment possessed potent synergistic effects with DOX and reversed ABCB1-mediated drug resistance. Notably, the most potent compound D1 merits multiple activities, including low cytotoxicity, the strongest synergistic effect, and effectively reversing ABCB1-mediated drug resistance of K562/ADR (RF = 1845.76) and MCF-7/ADR cells (RF = 207.86) to DOX. As a reference substance, compound D1 allows for additional mechanistic studies on ABCB1 inhibition. The synergistic mechanisms were mainly related to the increased intracellular accumulation of DOX via inhibiting the efflux function of ABCB1 rather than from affecting the expression level of ABCB1. These studies suggest that compound D1 and its derivatives might be potential MDR reversal agents acting as ABCB1 inhibitors in clinical therapeutics and provide insight into a design strategy for the development of ABCB1 inhibitors.

Design, synthesis, and bioactivity study on Lissodendrins B derivatives as PARP1 inhibitor.

Poly(ADP-ribose) polymerase-1 (PARP1) is an enzyme that catalyzes the polymerization of ADP-ribose units to target proteins, and it is a potential target for anti-cancer drug discovery, especially for BRAC1/2 mutated tumors. In this study, a series of 2-aminoimidazole Lissodendrins B derivatives were designed, synthesized, and evaluated as PARP1 inhibitors. We found that compound D3 is better due to its PARP enzyme inhibitory activity and in vitro anti-cancer activity compared with other tested compounds. It could inhibit PARP1 enzymatic activity (IC50 = 17.46 µM) in the non-cell system and BRCA1-deficient HCC1937 and MDA-MB-436 cells growth (IC50 = 17.81 and 12.63 µM, respectively). Further study demonstrated that compound D3 inhibits tumor growth through multiple mechanisms, such as reduction of PARylation, accumulation of cellular DNA double-strand breaks, induction of G2/M cell cycle arrest, and subsequent apoptosis of BRCA1-deficient cells. Besides, the molecular docking study also confirmed that compound D3 could effectively occupy the active pocket of PARP1. Our findings provide a new skeleton structure for PARP1 inhibitor, and the results suggested that the compound D3 may serve as a potential lead compound to develop novel PARP1 inhibitors for cancer therapy.

A prospective, single-arm, phase II clinical trial of intraoperative radiotherapy using a low-energy X-ray source for local advanced Laryngocarcinoma (ILAL): a study protocol.

BACKGROUND: Laryngocarcinoma (LC), in most cases a squamous cell carcinoma, accounts for 1 ~ 5% of the incidence of all tumors. At present, laryngocarcinoma is mainly managed with the integration of surgery and radio- and chemo-therapies. The current development trend of treatment is to improve the local control rate of tumor and the quality of life of patients. Intraoperative radiation therapy (IORT) is a radiotherapy that delivers single high dose irradiation at a close range to the tumor bed during the surgical operation process. It has particular radiobiological advantages in protecting normal surrounding tissues by directly applying the irradiation dose to the high-risk tumor bed area. Two forms of IORT, i.e., high dose rate (HDR) brachytherapy and external beam radiotherapy (EBRT, including electron and photono IORT), had been studied before the treatment of head and neck tumors (including laryngocarcinoma). However, no relevant assessment had been carried out on 50KV low-energy X-ray. We are convinced by certain arguments that the application of low-energy X-ray for intraoperative local radiotherapy of laryngocarcinoma can not only achieve the therapeutic effect of IORT but also reduce the incidence of high-energy irradiation related toxic and side effects. The purpose of this study is to observe the safety and short-term efficacy of IORT when used in conjunction with standard of care for the treatment of local advanced laryngocarcinoma (LAL). METHODS/DESIGN: In consideration of the applications of precise targeted IORT in oncosurgery and in line with the application range and reference clinical medical guidances approved by SFDA (ZEISS radiosurgical operation system has been used for the treatment of solid tumors since 31 December, 2013 with an approval from SFDA), we have preliminarily planned the tumors suitable for IORT, determined the members of MDT in our hospital, improved the MDT diagnosis and treatment processes for the tumors, established the standards, indications and contraindications for the application of IORT, determined the indicators to be observed after the treatment of tumors with surgical operations plus IORT, and carried out follow-up visits and statistical analysis. This is a single-arm, prospective Phase II clinical trial of the treatment of LAL patients with IORT + EBRT. The study subjects are followed up for statistics and information of their acute/chronic toxic reactions and local control rate, DFS, and OS etc. The safety and short-term efficacy of the application of IORT as SIB for the treatment of LAL. The sample size of the study is 125 subjects. DISCUSSION: The safety and efficacy of IORT for the treatment of head and neck cancers have been proven in studies by multiple institutions (1-3). The purpose of this study is to investigate the maximum safe dose and short-term efficacy of IORT for providing a theoretical basis for clinical trials. TRIAL REGISTRATION: Trial registration: Clinicaltrials.gov , NCT04278638. Registered 18 February 2020 - prospectively registered, https://clinicaltrials.gov/ct2/show/NCT04278638.

High throughput scanning of dimer interactions to facilitate confirmation of the molecular stacking mode: a case of 1,3,5-trinitrobenzene and its amino-derivatives.

Exactly predicting the packing structures of a given molecule is a crucial topic in crystal engineering, while it remains still challenging, as it requires huge calculations, largely above common computation cost and time limitations. However, current progress in high throughput calculations makes the fast screening of structures and properties feasible. In the present work, we exemplify this by considering a special case of ascertainment of the molecular stacking mode and shear properties of energetic materials. Four energetic π-bonded molecules, 1,3,5-trinitrobenzene, 2,4,6-trinitroaniline, 1,3-diamino-2,4,6-trinitrobenzene and 2,4,6-triamino-1,3,5-trinitrobenzene, with a different number of H atoms replaced by amino groups, are adopted as samples to scan the potential energy surfaces (PESs) of dimers through high throughput calculations. It is found that the parallel stacking mode is the most energetically favored, followed by the T-shaped, coplanar and crossing ones. Such an energetically favored stacking mode is observed in all related π-stacked crystal structures at ambient conditions or low temperatures. It shows that the stacking mode can be ascertained through the PES scanning of dimers, and thereby, the stacking structures and properties related to the stacking mode, like mechanical anisotropism, can be quickly screened by means of high throughput calculations.

Efficient Total Synthesis of Lissodendrin B, 2-Aminoimidazole Marine Alkaloids Isolated from Lissodendoryx (Acanthodoryx) Fibrosa.

Lissodendrin B is a 2-aminoimidazole alkaloid bearing a (p-hydroxyphenyl) glyoxal moiety that was isolated from the Indonesian sponge Lissodendoryx (Acanthodoryx) fibrosa. We reported the first efficient total synthesis of Lissodendrin B. The precursor 4,5-disubstituted imidazole was obtained through Suzuki coupling and Sonogashira coupling reactions from 4-iodoimidazole. C2-azidation and reduction of the azide then provided the core structures of Lissodendrin B. Subsequent triple-bond oxidation, demethylation, and deacetylation gave the final product. The synthesis approach consists of ten steps with an overall yield of 1.1% under mild reaction conditions, and it can be applied for future analog synthesis and biological studies.

A DFT Study Toward the Reaction Mechanisms of TNT With Hydroxyl Radicals for Advanced Oxidation Processes.

The degradation pathway of environmental contaminant 2,4,6-trinitrotoluene (TNT) was investigated computationally at the SMD(Pauling)/M06-2X/6-311+G(d,p) level of theory. The dominant decomposition pathway of TNT → 4,6-dinitro-o-cresol → 4,6-dinitro-2-hydroxybenzylalcohol → 4,6-dinitro-2-hydroxybenzaldehyde was provided, and the corresponding predicted products and their distributions are in a good agreement with available experimental data on TNT degradation by Fenton reaction. It was shown that the mechanism of addition-elimination is crucial for this stage of the reaction. The reaction of H atom abstraction is a minor competing pathway. The details on transition states, intermediate radicals, and free energy surfaces for all proposed reactions are given and make up for a lack of experimental knowledge.

Progesterone attenuates aquaporin-4 expression in an astrocyte model of ischemia/reperfusion.

Previous studies have suggested that progesterone may be involved in neuroprotection by preventing brain edema. In this study, we assessed the effects of progesterone on aquaporin-4 (AQP4) expression in an ischemia/reperfusion model of cultured rat astrocytes, and further explored the possible role of the protein kinase C (PKC) pathway in this course. We evaluate primary culture astrocytes exposed to 4 h oxygen-glucose deprivation (OGD) followed by 24 h reperfusion (OGD4h/R24h) as a means of simulating cortex ischemia and reperfusion, and test the effect of progesterone on AQP4 expression in response to OGD4h/R24h. Besides, the cell viability was assessed by MTT reduction and lactate dehydrogenase release assay, accompanied by cell morphology survey. At a concentration of 1 and 2 µM, progesterone significantly attenuated AQP4 at the level of both protein and mRNA and ameliorated the cell viability of astrocytes from OGD/reperfusion injury. Moreover, this effect was blocked by the PKC inhibitor Ro31-8220, which was employed before the OGD. These results indicate that progesterone exerts the protective effects and attenuates AQP4 expression in an astrocyte model of ischemia/reperfusion depending on the PKC signal pathway.

A physical organic strategy to predict and interpret stabilities of chemical bonds in energetic compounds for the discovery of thermal-resistant properties.

CONTEXT: The in-depth understanding about the stability of chemical bonds in energetic compounds plays a central role for molecular design and safety-related evaluations. Most energetic compounds contain nitro as explosophores, and nitro cleavage is fundamental for thermal and mechanical stability. However, the quantum chemistry approach to accurately predict energy and temperature properties related to bond stability is challenging, due to the tradeoff between computational costs and deviations. Herein, the bond orders are proposed as accurate and computational-cost efficient descriptors for predicting the chemical bond stability and thermal-resistant properties. The intrinsic bond strength index (IBSI) demonstrates the best prediction for experimental homolytic bond dissociation energies (R2 > 0.996), which is on par with the results from high-precision quantum chemistry methods. The effects from bond connectivity and steric hindrance hierarchy were analyzed to reveal underlying mechanisms. Additionally, the IBSI descriptors are successfully applied to predict the thermal decomposition temperatures of 24 heat-resistant energetic compounds (R2 = 0.995), thus validating the effectiveness for the prediction and interpretation of chemical bond stability in energetic compounds via a physical organic approach. METHODS: All DFT calculations were performed with Gaussian 09 software. To investigate the dependence of the method on functionals and basis sets, 9 DFT methods were considered (B3LYP/6-31G(d,p), B3LYP/6-311G(d,p), B3LYP/def2-TZVP, M062X/6-31G(d,p), M062X/6-311G(d,p), M062X/def2-TZVP, ωB97XD/6-31G(d,p), ωB97XD/6-311G(d,p), and ωB97XD/def2-TZVP). The bond order descriptors LBO and IBSI are obtained through the bond order analysis module in the Multiwfn software.

Correction to "Using Imidazo[2,1-b][1,3,4]thiadiazol Skeleton to Design and Synthesize Novel MNK Inhibitors".

[This corrects the article DOI: 10.1021/acsmedchemlett.2c00442.].

Using Imidazo[2,1-b][1,3,4]thiadiazol Skeleton to Design and Synthesize Novel MNK Inhibitors.

Mitogen-activated protein kinase-interacting protein kinases (MNKs) phosphorylate eukaryotic initiation factor 4E (eIF4E) and regulate the processes of cell proliferation, cell cycle, and migration and invasion of cancer cells. Selectively inhibiting the activity of MNKs could be effective in treating cancers. In this study, we report a series of novel MNK inhibitors with an imidazo[2,1-b][1,3,4]thiadiazol scaffold, from which, compound 18 inhibited the phosphorylation of eIF4E in various cancer cell lines potently. Compound 18 was more potent against MNK2 than MNK1, and decreased the levels of cyclin-B1, cyclin-D3, and MMP-3 in A549 and MDA-MB-231 cells, impaired cell growth and colony formation, arrested the cell cycle in the G0/G1 phase, and inhibited cell migration and the secretion of TNF-α, MCP-1, and IL-8 from A549 cells. It represents a starting compound to design further inhibitors that selectively target MNKs and apply in other diseases.

Ultrasensitive iodide detection in biofluids based on hot electron-induced reduction of p-Nitrothiophenol on Au@Ag core-shell nanoparticles.

Surveillance of iodine intake is important because either inadequate or excessive amount of iodine may lead to thyroid malfunctions. Herein, we report a method for fast iodide quantification based on a plasmonic hot electron-driven chemical reaction, which occurs on Au@Ag core-shell nanoparticles (NPs) coated with p-nitrothiophenol (PNTP) molecules. Upon resonant light illumination, hot electron-hole pairs are generated in the NPs. The hot holes capture iodide ions (I-) and form AgI which decomposes under light; while the hot electrons are shifted to the electron orbital (LUMO) of PNTP and trigger its reduction to p-aminothiophenol (PATP). By measuring characteristic surface-enhanced Raman spectroscopic (SERS) peaks of PNTP and PATP, the concentration of I- in water can be quantitatively determined, with a linear response in the 0.5-20 µM range and a detection limit of 0.30 µM. The Au@Ag nanosensor was then applied for I- detection in various biofluids including urine, serum and saliva, exhibiting superior detection sensitivity and high selectivity. This sensing assay requires a small sample volume of ∼10 µL and completes the entire detection process in ∼2 min, and therefore holds significant potential for application in point-of-care settings.

Dual-energy CT iodine map in predicting the efficacy of neoadjuvant chemotherapy for hypopharyngeal carcinoma: a preliminary study.

Neoadjuvant chemotherapy has become one of the important means for advanced hypopharyngeal carcinoma. So far, there is no effective index to predict the curative effect. To investigate the value of iodine map of dual-energy computed tomography (CT) in predicting the efficacy of neoadjuvant chemotherapy for hypopharyngeal carcinoma. A total of 54 hypopharyngeal carcinomapatients who underwent two courses of TPF neoadjuvant chemotherapy were recruited in this study. Three cases had a complete response (CR), thirty-six cases had a partial response (PR), eleven cases had stable disease (SD), and four cases had a progressive disease (PD) after the chemotherapy. All patients underwent a dual-source CT scan before chemotherapy and rescanned after chemotherapy. The normalized iodine-related attenuation (NIRA) of the mean of maximum slice and most enhanced region of lesion at arterial and parenchymal phase were measured: NIRAmean-A, NIRAmax-A, NIRAmean-P, and NIRAmax-P, respectively. Correlation analysis was conducted between different metrics of NIRA and the diameter change rate of lesions, and the curative effect was evaluated based on the receiver operating characteristic (ROC) curve. There were a significant correlation between NIRAmean-A, NIRAmax-A, NIRAmean-P, NIRAmax-P and the change rate of lesion's maximum diameter (ΔD%) (all P < 0.01). The NIRAmax-A, NIRAmean-P, NIRAmax-P had significant differences between CR, PR, SD, PD groups, but NIRAmean-A did not reach a significant difference. All NIRAmean-A, NIRAmax-A, NIRAmean-P, NIRAmax-P had significant differences between effective (CR + PR) and ineffective (SD + PD) groups. The ROC analysis revealed that NIRAmean-P had the largest AUC and prediction efficacy (AUC = 0.809). Dual-energy CT iodine map could predict the efficacy of neoadjuvant chemotherapy and provides imaging evidence to assist in treatment decisions for hypopharyngeal carcinoma patients.

Immunomodulatory activity of butanol extract from Solanum lyratum in tumor-bearing mice.

Solanum lyratum Thunb (Solanaceae) has been widely used for cancer as a folk remedy in Chinese traditional medicine. In this study, the main active fraction n-butanol extract from S. lyratum (BESL) was evaluated for the therapeutic efficacies on mice transplantable tumor and immunomodulatory potentials on the immune response in tumor-bearing mice. The effects of BESL on the growth of mouse transplantable S180 sarcoma, splenocyte proliferation, the activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL), production of cytokines from splenocytes, and serum antigen-specific antibody levels in S180-bearing mice were measured. BESL could not only significantly inhibit the growth of S180 sarcoma transplanted in mice, but also remarkably promote splenocytes proliferation, NK cell and CTL activity, interleukin-2 and interferon-γ production from splenocytes, and serum antigen-specific antibody levels in tumor-bearing mice (P < 0.05, P < 0.01, or P <0.001). The results suggested that BESL might exhibit antitumor activity by improving immune response, and it could act as antitumor agent with immunomodulatory activity. This study provided evidence to understand the therapeutic effects of S. lyratum for treatment of cancer and a natural product to further researches to be developed as a cancer chemopreventive agent.

Two cases of rare thyroid malignancy-case report.

We report 2 cases of rare thyroid malignancy: angiosarcoma and myoepithelial carcinoma (MC). Thyroid angiosarcomas (TAS) is extremely rare and comprises less than 1% of primary thyroid cancer worldwide. MC usually presents as a slow-growing painless mass arising in the salivary glands. It has not been reported in the thyroid gland. The first case describes a 59-year-old patient who was admitted to hospital with the discovery of thyroid nodule for 1 month. The tumor thrombus was found in the left internal jugular vein and superior thyroid artery during the operation. Diagnosis of angiosarcoma of the thyroid was based on positive endothelial markers such as thrombomodulin and CD31 after total thyroidectomy. The left internal jugular vein, left recurrent laryngeal nerve and anterior cervical banding muscle were invaded by thyroid tumor. No lymph node metastasis was observed. The patient died after 4 years. The second case describes a 55-year-old woman who presented with the discovery of thyroid nodule for 1 month. Right thyroid lobectomy and right neck lymph node functional dissection were carried out. The results from postoperative pathology revealed that papillary carcinoma in right lobe of thyroid and MC next to thyroid were found. Besides, the metastasis of MC was observed at right II-IV level and right VI level. Five years later, the patient was re-admitted to hospital, primarily due to the discovery of anterior cervical tumor for one year. Then, she underwent left thyroid lobectomy and right tumor resection. Postoperative routine pathology showed recurrent MC in the right thyroid. After surgery and radiotherapy, the patient was followed up for 2 years. Angiosarcoma and myoepithelioma should be kept in mind in diagnosis of thyroid malignant tumor.

Neoadjuvant chemotherapy as a comprehensive treatment in patients with laryngeal and hypopharyngeal carcinoma.

Background: Neoadjuvant chemotherapy is important for advanced laryngeal and hypopharyngeal carcinoma (LHC).Aims/objectives: To determine the efficacy and toxicity of the combination of docetaxel, nedaplatin, and 5-fluorouracil in induction treatment of advanced LHC.Material and methods: A total of 157 cancer patients were included. The primary endpoints of this study were overall response rate, pathological complete response rate, the safety of induction treatment, progression-free survival (PFS), and overall survival (OS).Results: After two-cycle induction treatment, 17(10.8%) patients experienced complete remission, 76 (48.4%) experienced partial remission, 47 (30.0%) had stable disease, and 17 (10.8%) had progressive disease. The TNM stage decreased by two or more in 17 cases, decreased by one in 71 cases, increased in 15 cases, and did not change in 54 cases after induction treatment. Most of the adverse chemotherapy responses were alleviated by symptomatic management. After the induction treatment, 29 patients continued receiving chemotherapy followed by radiotherapy, and 112 underwent surgical management depending on tumor site followed by radiotherapy. The median PFS was 13.00 ± 2.10 months and the median OS was 14.20 ± 0.29 months.Conclusions and significance: Combination of docetaxel, nedaplatin, and 5-fluorouracil plays an important role in the comprehensive treatment of advanced LHC.

Strategy for chemically riveting catenated nitrogen chains.

Catenated nitrogen chains (CNCs) attract considerable attention because of their structural novelty, their high energy, and their potential as precursors for all-nitrogen materials. However, pure CNCs are unstable under ambient conditions, limiting their on-site or practical applications. Chemical riveting of a CNC involves the maintenance of the structure of a CNC and placing the CNC in a special chemical structure as a moiety of an entire molecule to stabilize it. Other structures, except from the CNC, are named rivets. In this study, the molecular geometry, bond order, natural bond orbital charge, and frontier orbital among the pure CNCs (Nx), Nx-, Nx+, and NxHy (x = 2-11) and CNCs riveted and implemented experimentally in several former studies are systematically analyzed and compared. The lone-pair repulsion between two neighboring N atoms is one of the primary factors for the low molecular stability of the pure CNCs and their derivatives. The riveted CNCs with rings are usually more stable than those with open chains. Moreover, the standard deviation of the bond orders or the bond lengths can be employed as an indicator for molecular stability, i.e., a lower standard deviation suggests higher molecular stability. Hence, electron-donating groups, groups with electronegativity within those of H and N atoms, as well as atoms or groups with empty orbitals are proposed to trap the lone pairs of CNCs as rivets to stabilize the CNCs. This strategy is expected to facilitate the creation of stable CNC-contained compounds with high structural novelty or high energy contents. Graphical abstractA strategy is proposed for chemically riveting instable CNCs to transform them into more stable ones.

Accuracy of computer-aided geometric three-dimensional reconstruction of the human petrous bone based on serial unstained celloidin sections.

The aim of this study was to present a comprehensive three-dimensional (3D) morphology of the petrous bone with computer image-processing technology, which could be beneficial for the teaching of anatomy and for surgical procedures. The unstained celloidin sections of human temporal bone were digitized with high resolution and quality, and then processed with Amira® software to include alignment, segmentation and reconstruction. The integral structure of the human inner ear was presented with computer modeling, including the petrous bone, bone labyrinth, internal carotid artery canal, internal jugular vein canal, sigmoid sinus, inferior petrosal sinus, glossopharyngeal meatus, vagal meatus, internal acoustic meatus, facial nerve canal, greater superficial petrosal nerve, vestibular aqueduct, extraosseous portion of the endolymphatic sac, round and oval window, processus cochleariformis and pyramidal eminence. The 3D model showed detailed structure of the external and internal petrous bone, as well as their spatial relationship. The present study suggests the feasibility of comprehensive 3D reconstruction of the petrous bone using unstained celloidin sections, which may provide advantages for future study.

[Clinical application of endoscopy-assisted resection of tumors in parapharyngeal space].

OBJECTIVE: To explore the advancement of the endoscopic video system in parapharyngeal space tumor resection. METHODS: Thirty cases parapharyngeal space tumor patients underwent endoscopy-assisted tumors resection in otorhinolaryngology-head and neck surgery of Tianjin First Central Hospital. The passway included trans-oral cavity in 6 cases, 21 cases with trans-neck side and trans-neck-parotid gland in 3 cases. RESULTS: Tumors of all cases were completely resected, without residual tumor. It was included 23 cases of benign tumors (14 cases of parotid pleomorphic adenoma, 8 cases of neurilemmoma, lymph node tuberculosis in 1 case), malignant tumor in 7 cases (2 cases of metastatic carcinoma, 2 cases of malignant mixed tumor, 1 case of malignant neurilemmoma, 2 cases of adenoid cystic carcinoma). Tongue deflection was recorded in 2 cases. There were neither wound infection or bleeding. All the cases were followed up after operation without recurrence. Seven cases of malignant tumor patients were all alive with follow-up 1 year in 1 case, 3 years in 4 cases, 2 cases for five years. CONCLUSIONS: Endoscopy-assisted tumors resection can deal with visual lesion corner and allow previous part no visibility surgery into all operation under direct vision. It contributed to improve the quality of operation, reduce the surgery complication. It was worth to be wide spreaded in clinic.

[The long-term morphology of the nasal cavity after total laryngectomy].

OBJECTIVE: To investigate the long-term effect of nasal airflow deprivation on nasal dimensions after total laryngectomy. METHOD: Thirty-two patients with total laryngectomy were enrolled in the study. Acoustic rhinometry was used to measure the minimum cross-sectional area (MCSA) and the volume of the nasal cavity after laryngectomy, compared with the normal control group. In addition, patients underwent endoscopic nasal examinations and answered questionnaires postoperatively, symptoms between the different levels to compare the results of acoustic rhinometry. RESULT: At both within 1-year and more than 1-year follow-ups, the mean MCSAs and the mean nasal volumes were significantly expanded than the control values (P < 0.05). The nasal MCSA, nasal cavity volume was no significant difference between more than one year and less than 1 year group (P > 0.05). The endoscopic examinations revealed only a deterioration in the appearance of the nasal mucosa over the long term. Survey showed that the postoperative patients had varying degrees of nasal obstruction flu, nose dry, hyposmia, etc. The nasal MCSA, nasal cavity volume was of the largest when moderate nasal obstruction flu,or severe dry nose or severe hyposmia. CONCLUSION: The structure was atrophic nasal change, the nasal MCSA, nasal cavity volume were larger, the results of acoustic rhinometry was different among the varying degrees of symptoms after total laryngectomy.

[Objective evaluation of nasal ventilation function in healthy adults in Tianjin area].

OBJECTIVE: To establish reference values of acoustic rhinometry, rhinomanometry and rhinospirometer in healthy adults in Tianjin area, analyze the effects of age,sex and side on the value, investigate the correlation of the measure values, offer the diagnosis date for test nasal ventilation function in Tianjin area. METHOD: Four hundred and sixty-six healthy adults in Tianjin area were tested. A1 acoustic rhinometry was used to measure the minimum cross-sectional area (MCA), distance of the minimal cross-sectional area to the nostril (DCAN) and the nasal volume from 0-5 cm, 2-5 cm (V5, V2-5); At 150 Pa, 75 Pa and broms, NR6 Rhinomanometry was used to measure unilateral nasal inspiratory resistance (IR)and expiratory resistance (ER), bilateral nasal inspiratory and expiratory resistance (TIR and TER), and differences of the bilateral nasal resistance can be calculated; NV1 Rhinospirometer was used to measure unilateral inspiratory capacity (IC) and expiration capacity (EC), and the nasal partitioning ratio (NPR) can be calculated. Practical measure the distance of nostril to ahead of the inferior turbinate and compare with DCAN. Make the correlational analysis on different index of three exam. RESULT: Reference values of acoustic rhinometry: MCA was (0.45 +/- 0. 16) cm2 for male, (0.44 +/- 0.16) cm2 for female; V2-5 was (3.52 +/- 1.38) cm3 for male, (3.36 +/- 1.22) cm3 for female, V5 was (5.10 +/- 1.47) cm3 for male, (4.86 +/- 1.12) cm3 for female; DCAN have two distance, (2.22 +/- 0.398, 0.53 +/- 0.625) cm was for male, (2.10 +/- 0.37, 0.67 +/- 0.15) cm was for female. No significant gender, side and age differences were shown in MCA, V5, V2-5. Significant gender differences were shown in DCAN but no side and age differences. Reference values of rhinomanometry: Significant gender but no side and age differences were shown in IR, ER, TIR, TER. Reference values of rhinospirometer: IC was (2.06 +/- 1.10) L/20 s for male, (1.37 +/- 0.34) L/20 s for female, EC was (2.15 +/- 1.23) L/20 s for male (1.39 +/- 0.58) L/20 s for female. NPRi was 0.11 [0.05, 0.23],NPRe was 0.11 [0.05, 0.19]. Significant gender but no side and age differences were shown in IC and EC. No gender and age differences were shown in NPRi and NPRe. There was significant correlation found between MCA and IR/ER/IC/EC, IR and IC, ER and EC, Rlr and NPRi/ NPRe. CONCLUSION: Acoustic rhinometry,rhinomanometry and rhinospirometer can be useful reference values to evaluate nasal ventilation function, more value will be found if use the three together.