Genome-wide identification, expression analysis, and abiotic stress response of the CBL and CIPK gene families in Artocarpus nanchuanensis.

Artocarpus nanchuanensis, the northernmost species in the jackfruit genus, has great economic and horticultural value due to its nutritious fruit and beautiful tree shape. Calcineurin B-like proteins (CBLs) act as plant-specific Ca2+ sensors and participate in regulating plant responses to various abiotic stresses by interacting with CBL-interacting protein kinases (CIPKs). However, the characteristics and functions of the CBL and CIPK genes in A. nanchuanensis are still unclear. Here, we identified 14 CBL and 33 CIPK genes from the A. nanchuanensis genome, and based on phylogenetic analysis, they were divided into 4 and 7 clades, respectively. Gene structure and motif analysis indicated that the AnCBL and AnCIPK genes were relatively conserved. Colinear analysis showed that segmental duplication contributed to the expansion of the AnCBL and AnCIPK gene families. Expression analysis showed that AnCBL and AnCIPK genes were widely expressed in various tissues of A. nanchuanensis and exhibited tissue-specific expression. In addition, three genes (AnCBL6, AnCIPK7/8) may play important roles in response to salt, cold, and drought stresses. In summary, this study lays an important foundation for the improvement of stress resistance in A. nanchuanensis and provides new insight for the functional research on CBL and CIPK gene families.

CENPN suppresses autophagy and increases paclitaxel resistance in nasopharyngeal carcinoma cells by inhibiting the CREB-VAMP8 signaling axis.

Chemotherapeutic resistance is one of the most common reasons for poor prognosis of patients with nasopharyngeal carcinoma (NPC). We found that CENPN can promote the growth, proliferation and apoptosis resistance of NPC cells, but its relationship with chemotherapeutic resistance in NPC is unclear. Here we verified that the CENPN expression level in NPC patients was positively correlated with the degree of paclitaxel (PTX) resistance and a poor prognosis through analysis of clinical cases. VAMP8 expression was significantly increased after knockdown of CENPN by transcriptome sequencing. We found in cell experiments that CENPN inhibited macroautophagy/autophagy and VAMP8 expression and significantly increased PTX resistance. Overexpression of CENPN reduced the inhibitory effects of PTX on survival, cell proliferation, cell cycle progression and apoptosis resistance in NPC cells by inhibiting autophagy. In turn, knockdown of CENPN can affect the phenotype of NPC cells by increasing autophagy to achieve PTX sensitization. Sequential knockdown of CENPN and VAMP8 reversed the PTX-sensitizing effect of CENPN knockdown alone. Experiments in nude mice confirmed that knockdown of CENPN can increase VAMP8 expression, enhance autophagy and increase the sensitivity of NPC cells to PTX. Mechanistic studies showed that CENPN inhibited the translocation of p-CREB into the nucleus of NPC cells, resulting in the decreased binding of p-CREB to the VAMP8 promoter, thereby inhibiting the transcription of VAMP8. These results demonstrate that CENPN may be a marker for predicting chemotherapeutic efficacy and a potential target for inducing chemosensitization to agents such as PTX.Abbreviations: 3-MA: 3-methyladenine; ATG5: autophagy related 5; CENPN: centromere protein N; CQ: chloroquine; CREB: cAMP responsive element binding protein; ChIP: chromatin immunoprecipitation assay; IC50: half-maximal inhibitory concentration; LAMP2A: lysosomal associated membrane protein 2A; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NPC: nasopharyngeal carcinoma; NPG: nasopharyngitis; oeCENPN: overexpressed CENPN; PTX: paclitaxel; RAPA: rapamycin; RNA-seq: transcriptome sequencing; shCENPN: small hairpin RNA expression vector targeting the human CENPN gene; shCENPN-shVAMP8: sequential knockdown targeting the human CENPN gene and VAMP8 gene; shVAMP8: small hairpin RNA expression vector targeting the human VAMP8 gene; TEM: transmission electron microscopy; TIR: tumor inhibitory rate; VAMP8: vesicle associated membrane protein 8.

High homocysteine levels as potential indicators of subacute combined degeneration of the spinal cord.

BACKGROUND: Homocysteine (Hcy) is widely recognized as a significant risk factor for cardiovascular and cerebrovascular diseases. However, our research has uncovered a novel perspective, suggesting that elevated levels of Hcy could serve as an indicator for neurological diseases. This article presents a unique case of Subacute Combined Degeneration of the spinal cord(SCD), characterized by high homocysteine levels, yet normal vitamin B12 and imaging results. This discovery could facilitate early detection and ensure timely referral of patients to specialized departments for further treatment.

Enhancing nasopharyngeal carcinoma cell radiosensitivity by suppressing AKT/mTOR via CENP-N knockdown.

OBJECTIVE: Investigating the impact of centromere protein N (CENP-N) on radiosensitivity of nasopharyngeal carcinoma (NPC) cells. METHODS: Using immunohistochemistry and immunofluorescence to detect CENP-N expression in tissues from 35 patients with radiosensitive or radioresistant NPC. Assessing the effect of combined CENP-N knockdown and radiotherapy on various cellular processes by CCK-8, colony formation, flow cytometry, and Western blotting. Establishing a NPC xenograft model. When the tumor volume reached 100 mm3, a irradiation dose of 6 Gy was given, and the effects of the combined treatment were evaluated in vivo using immunofluorescence and Western blotting techniques. RESULTS: The level of CENP-N was significantly reduced in radiosensitive tissues of NPC (p < 0.05). Knockdown of CENP-N enhanced NPC radiosensitivity, resulting in sensitizing enhancement ratios (SER) of 1.44 (5-8 F) and 1.16 (CNE-2Z). The combined treatment showed significantly higher levels of proliferation suppression, apoptosis, and G2/M phase arrest (p < 0.01) compared to either CENP-N knockdown alone or radiotherapy alone. The combined treatment group showed the highest increase in Bax and γH2AX protein levels, whereas the protein Cyclin D1 exhibited the greatest decrease (p < 0.01). However, the above changes were reversed after treatment with AKT activator SC79. In vivo, the mean volume and weight of tumors in the radiotherapy group were 182 ± 54 mm3 and 0.16 ± 0.03 g. The mean tumor volume and weight in the combined treatment group were 84 ± 42 mm3 and 0.04 ± 0.01 g. CONCLUSION: Knockdown of CENP-N can enhance NPC radiosensitivity by inhibiting AKT/mTOR.

The genetic structure and demographic history revealed by whole-genome resequencing provide insights into conservation of critically endangered Artocarpus nanchuanensis.

Introduction: Whole-genome resequencing technology covers almost all nucleotide variations in the genome, which makes it possible to carry out conservation genomics research on endangered species at the whole-genome level. Methods: In this study, based on the whole-genome resequencing data of 101 critically endangered Artocarpus nanchuanensis individuals, we evaluated the genetic diversity and population structure, inferred the demographic history and genetic load, predicted the potential distributions in the past, present and future, and classified conservation units to propose targeted suggestions for the conservation of this critically endangered species. Results: Whole-genome resequencing for A. nanchuanensis generated approximately 2 Tb of data. Based on abundant mutation sites (25,312,571 single nucleotide polymorphisms sites), we revealed that the average genetic diversity (nucleotide diversity, π) of different populations of A. nanchuanensis was relatively low compared with other trees that have been studied. And we also revealed that the NHZ and QJT populations harboured unique genetic backgrounds and were significantly separated from the other five populations. In addition, positive genetic selective signals, significantly enriched in biological processes related to terpene synthesis, were identified in the NHZ population. The analysis of demographic history of A. nanchuanensis revealed the existence of three genetic bottleneck events. Moreover, abundant genetic loads (48.56% protein-coding genes) were identified in Artocarpus nanchuanensis, especially in genes related to early development and immune function of plants. The predication analysis of suitable habitat areas indicated that the past suitable habitat areas shifted from the north to the south due to global temperature decline. However, in the future, the actual distribution area of A. nanchuanensis will still maintain high suitability. Discussion: Based on total analyses, we divided the populations of A. nanchuanensis into four conservation units and proposed a number of practical management suggestions for each conservation unit. Overall, our study provides meaningful guidance for the protection of A. nanchuanensis and important insight into conservation genomics research.

Qualification of Pilots with Aero-Otitis Media After Balloon Eustachian Tuboplasty.

BACKGROUND: Aero-otitis media (AOM), also known as aural barotrauma or barotitis media, is categorized into primary AOM and secondary AOM. Because conservative treatment was ineffective, primary AOM was one of the main reasons for grounding. In 2014, the team successfully treated a pilot with primary AOM using balloon Eustachian tuboplasty (BET). Now, this case is reported.CASE REPORT:The patient was a 40-yr-old male transport pilot who joined a flight after catching a cold. During the descent, the right ear appeared to have stuffiness and hearing loss, accompanied by tinnitus and ear pain. The local hospital's acoustic immittance test showed an "A" curve in the left ear and a "B" curve in the right ear. According to "secretory otitis media", right tympanic membrane puncture and drugs were performed. After he recovered, he continued to fly, and the symptoms reappeared again. Then he was transferred to our hospital, and right BET was performed. Equalization of ear pressure in the hypobaric chamber returned to normal 2 mo after the operation. The pilot was found fit to fly. The pilot is still qualified, with more than 6000 h of flight time.DISCUSSION: AOM is linked to Eustachian tube dysfunction. BET has been a minimally invasive treatment of Eustachian tube lesions in recent years. If conservative treatments for primary AOM are ineffective, BET can be selected. While the postoperative symptoms disappeared, pure tone audiometry, tympanometry, and ear pressure function tests met the standards for the physical examination of pilots, allowing the determination of flight qualification.Zhang M, Liu X, Wang B, Jin Z, Xu X. Qualification of pilots with aero-otitis media after balloon Eustachian tuboplasty. Aerosp Med Hum Perform. 2023; 94(8):629-633.

Complete mitochondrial genome of Thuja sutchuenensis and its implications on evolutionary analysis of complex mitogenome architecture in Cupressaceae.

BACKGROUND: The complex physical structure and abundant repeat sequences make it difficult to assemble the mitogenomes of seed plants, especially gymnosperms. Only approximately 33 mitogenomes of gymnosperms have been reported. However, as the most widely distributed and the second largest family among gymnosperms, Cupressaceae has only six assembled mitogenomes, including five draft mitogenomes and one complete mitogenome, which has greatly hindered the understanding of mitogenome evolution within this large family, even gymnosperms. RESULTS: In this study, we assembled and validated the complete mitogenome of Thuja sutchuenensis, with a size of 2.4 Mb. Multiple sequence units constituted its complex structure, which can be reduced to three linear contigs and one small circular contig. The analysis of repeat sequences indicated that the numbers of simple sequence repeats increased during the evolutionary history of gymnosperms, and the mitogenome of Thuja sutchuenensis harboured abundant extra-long repeats (more than 5 kb). Additionally, the longest repeat sequence identified in these seven gymnosperms also came from the mitogenome of Thuja sutchuenensis, with a length of up to 47 kb. The analysis of colinear blocks and gene clusters both revealed that the orders of mitochondrial genes within gymnosperms was not conserved. The comparative analysis showed that only four tRNAs were shared by seven gymnosperms, namely, trnD-GUC, trnE-UUC, trnI-CAU and trnY-GUA. Furthermore, four genes have undergone potential positive selection in most gymnosperm species, namely, atp8, ccmB, mttB and sdh4. CONCLUSION: We successfully assembled the second complete mitogenome within Cupressaceae and verified that it consisted of multiple sequence units. Our study also indicated that abundant long repeats may contribute to the generation of the complex conformation of the mitogenome of Thuja sutchuenensis. The investigation of Thuja sutchuenensis's mitogenome in our study provides new insight into further understanding the complex mitogenome architecture within gymnosperms.

Flumatinib plus venetoclax as an effective therapy for Philadelphia chromosome-positive acute myeloid leukemia: A case report.

Philadelphia chromosome-positive acute myeloid leukemia (Ph + AML) is a rare type of AML with a low survival rate and poor prognosis. We first report a Ph + AML patient who remained in long-term remission after the combination of flumatinib and venetoclax, which could provide corresponding treatment ideas for clinical practice.

Combination of Venetoclax and Midostaurin Efficiently Suppressed Relapsed t(8;21)Acute Myeloid Leukemia With Mutant KIT After Failure of Venetoclax Plus Azacitidine Treatment.

Acute myeloid leukemia (AML) with t(8;21) is categorized as favorable-risk AML, but KIT mutations show a significantly poor prognostic impact in such patients. Persistent vulnerability to relapse is a major challenge in the treatment of this subtype of patients. Venetoclax is a BCL-2 selective inhibitor. The venetoclax+HMA strategy is also a notable salvage regimen that achieves good clinical outcomes in the treatment of relapsed or refractory (R/R) AML. However, in our clinical practice, we found that disease progressed rapidly even after venetoclax+azacitidine (AZA) therapy in two relapsed t(8;21) AML patients with KIT mutations. We report for the first time the therapeutic potential of venetoclax+midostaurin as a new combination therapy for relapsed t(8;21) AMLs with KIT mutations showing resistance to venetoclax+AZA therapy. Our ex vivo study also showed that midostaurin alone could inhibit proliferation and induce apoptosis of Kasumi-1 cells (e.g. Midostaurin induced G2 phase cell arrest, down-regulated p-KIT and BCL-2, while Bax protein levels were up-regulated) and observed a synergistic anti effect when the two drugs were combined. Our study shows that the venetoclax+midostaurin regimen may be a promising treatment option for R/R t(8;21) AML with KIT mutations.

A Combined Histone Deacetylases Targeting Strategy to Overcome Venetoclax Plus Azacitidine Regimen Resistance in Acute Myeloid Leukaemia: Three Case Reports.

The management of patients with relapsed or refractory (R/R) acute myeloid leukaemia (AML) remains a challenge with few reliably effective treatments. Chidamide, a new selective HDAC inhibitor, has demonstrated some effectiveness in AML patients. Herein, we reported three patients with R/R AML who were unresponsive to venetoclax plus azacitidine (VA) but were successfully treated with VA when chidamide was added to the regimen. MCL1 is one of the anti-apoptotic proteins. Chidamide targets the MCL1 protein, which may permit venetoclax resistance when upregulated. We determined MCL1 protein expression in different AML cell lines, and chidamide could downregulate MCL1 expression in venetoclax resistance AML cells. In general, our experience showed that the chidamide/VA combination could improve the condition of R/R AML patients who are resistant to VA. Formally evaluating this regimen in R/R AML patients may be meaningful.

Factors affecting recurrent positive RT-PCR results in clinically cured COVID-19 patients: a multicenter study.

The aim of this study was to evaluate factors affecting the recurrence of positive RT-PCR results. By performing a retrospective analysis, we evaluated the clinical data of recurrent positive coronavirus disease 2019 (COVID-19) patients in multiple medical institutions in Wuhan. We recruited COVID-19 patients who were hospitalized from January 1 to March 10, 2020, in three tertiary hospitals in Wuhan, met the discharge criteria and received at least one additional nucleic acid test before leaving the hospital. According to the RT-PCR results, patients were split into a recurrent positive group (RPos group) and a nonrecurrent positive group (non-RPos group). Clinical characteristics, therapeutic schedules and antibody titers were compared between the two groups. AI-assisted chest high-resolution computed tomography (HRCT) technology was applied to investigate pulmonary inflammatory exudation and compare the extent of lung areas with different densities. This study involved 122 COVID-19 patients. There were no significant differences in age, sex, preexisting diseases, clinical symptoms, clinical classification, course of disease, therapeutic schedules or serum-specific antibodies between the two groups. A higher proportion of patients who showed pulmonary inflammatory exudation on HRCT scans were recurrent positive at the time of discharge than other patients (81.6% vs 13.7%, P < 0.01). In addition, the degree of pulmonary fibrosis was higher in the RPos group than in the non-RPos group (P < 0.05). Subpleural exudation at the peripheral edge of the lung and extensive pulmonary fibrosis at the time of discharge represent risk factors for the recurrence of COVID-19.

The characteristics and evolution of pulmonary fibrosis in COVID-19 patients as assessed by AI-assisted chest HRCT.

The characteristics and evolution of pulmonary fibrosis in patients with coronavirus disease 2019 (COVID-19) have not been adequately studied. AI-assisted chest high-resolution computed tomography (HRCT) was used to investigate the proportion of COVID-19 patients with pulmonary fibrosis, the relationship between the degree of fibrosis and the clinical classification of COVID-19, the characteristics of and risk factors for pulmonary fibrosis, and the evolution of pulmonary fibrosis after discharge. The incidence of pulmonary fibrosis in patients with severe or critical COVID-19 was significantly higher than that in patients with moderate COVID-19. There were significant differences in the degree of pulmonary inflammation and the extent of the affected area among patients with mild, moderate and severe pulmonary fibrosis. The IL-6 level in the acute stage and albumin level were independent risk factors for pulmonary fibrosis. Ground-glass opacities, linear opacities, interlobular septal thickening, reticulation, honeycombing, bronchiectasis and the extent of the affected area were significantly improved 30, 60 and 90 days after discharge compared with at discharge. The more severe the clinical classification of COVID-19, the more severe the residual pulmonary fibrosis was; however, in most patients, pulmonary fibrosis was improved or even resolved within 90 days after discharge.

SP1-induced AFAP1-AS1 contributes to proliferation and invasion by regulating miR-497-5p/CELF1 pathway in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma is a type of otolaryngological malignancy with high incidence. Long non-coding RNAs (lncRNAs) are closely related to nasopharyngeal carcinoma. LncRNA AFAP1-AS1 (AFAP1-AS1) has been found to play important roles in nasopharyngeal carcinoma progression and poor prognosis. However, the mechanism underlying AFAP1-AS1 in regulating nasopharyngeal carcinoma is still unclear. In current study, AFAP1-AS1 was found to be up-regulated in nasopharyngeal carcinoma tissues and cells. AFAP1-AS1 overexpression and knockdown were conducted in nasopharyngeal carcinoma cells. The results proved that AFAP1-AS1 promoted the survival and migration of nasopharyngeal carcinoma cells. Additionally, specificity protein 1 (SP1) was enhanced in nasopharyngeal carcinoma tissues and cells, and induced AFAP1-AS1 expression. The interaction between AFAP1-AS1 and miR-497-5p was confirmed. AFAP1-AS1 was demonstrated to regulate CELF1, a target gene of miR-497-5p. Further functional analysis revealed that AFAP1-AS1 knockdown attenuated SP1-induced nasopharyngeal carcinoma progression. These results indicate that SP1-induced AFAP1-AS1 facilitates nasopharyngeal carcinoma progression by regulating miR-497-5p/CELF1 pathway, which provides a new target for nasopharyngeal carcinoma treatment.

The Issue of Recurrently Positive Patients Who Recovered From COVID-19 According to the Current Discharge Criteria: Investigation of Patients from Multiple Medical Institutions in Wuhan, China.

The current discharge criteria for COVID-19 require that patients have 2 consecutive negative results for reverse transcription polymerase chain reaction (RT-PCR) detection. Here, we observed that recurrent positive RT-PCR test results in patients with 3 consecutive negative results (5.4%) were significantly decreased compared with those in patients with 2 consecutive negative results (20.6%); such patients reported positive RT-PCR test results within 1 to 12 days after meeting the discharge criteria. These results confirmed that many recovered patients could show a positive RT-PCR test result, and most of these patients could be identified by an additional RT-PCR test prior to discharge.

The association between vitamin deficiency and otolaryngologic diseases: A therapeutic target.

Vitamins are indispensable nutrients for metabolism. Adequate vitamin intake plays vital role in physiological processes including embryonic development, cellular and immunity proliferation and differentiation, DNA synthesis and oxidative response. In contrast, insufficient vitamin levels usually lead to a large number of clinical manifestations including xerophthalmia, nyctalopia, hyperpigmentation, vitiligo, jaundice, megaloblastic anemia, glossitis, scurvy, stroke, cancer, coronary heart disease, Alzheimer's disease, multiple sclerosis and Parkinson's disease. In recent years, more and more researches have focused on the relationship between vitamin family and otorhinolaryngologic diseases. This review will summarize the current knowledge of vitamin family and vitamin-mediated regulating role in those related otorhinolaryngologic diseases.

Dynamic Rabbit Model of Ear Barotrauma.

BACKGROUND: Establishing animal models of ear barotrauma (EB) to provide evaluation criteria for Eustachian tube dysfunction.METHODS: Using expansive sponges, 70 rabbits' right pharyngeal openings of the auditory tubes were blocked to cause dysfunction in the right Eustachian tubes. The right tympanic cavities of 65 rabbits were the Model Group (Subgroups 1-13) and these rabbits' left tympanic cavities were the Nonblockage Group. Hypobaric chamber tests (HCTs) at various vertical speeds (100 m · s-1, 75 m · s-1, 50 m · s-1, and 15 m · s-1) and altitudes (13,123 ft and 6562 ft) were conducted. The remaining five rabbits' right tympanic cavities were the Control Group and no HCTs were conducted. After HCTs, observations were made on rabbits' behavioral changes, oto-endoscope and tympanometry results, and pathological changes of the tympanic mucosae.RESULTS: 1) Rabbits in Subgroups 1-12 demonstrated EB, while Subgroup 13 and the Control Group did not. 2) Histopathology showed EB caused by rapid ascent/descent at 100 m · s-1 was more severe than that of 75 m · s-1 and 50 m · s-1 (P < 0.01), and that there were no significant differences in EB caused by rapid ascent/descent at 75 m · s-1 and 50 m · s-1 (P > 0.05). There were no significant differences in pathological injuries at the altitudes of 6562 ft and 13,123 ft (P > 0.05). 3) Based on tympanic membrane structures, tympanometry, and histopathological results, rabbits' EB can be classified into mild, moderate, and severe.DISCUSSION: EB's dynamic models could be established through HCTs on rabbits with Eustachian tube dysfunction.Wang B, Xu X, Lin J, Jin Z. Dynamic rabbit model of ear barotrauma. Aerosp Med Hum Perform. 2019; 90(8):696-702.

Carbon Dioxide Laser Microsurgery versus Low-Temperature Plasma Radiofrequency Ablation for T1a Glottic Cancer: A Single-Blind Randomized Clinical Trial.

BACKGROUND: Very few studies have been conducted to compare carbon dioxide laser microsurgery (CO2-LS) with low-temperature plasma radiofrequency ablation (LTP-RFA) in treating T1a glottic cancer. Therefore, we conducted this study to compare the efficacy of CO2-LS and LTP-RFA to define a superior therapeutic modality for T1a glottic cancer. METHODS: Patients (n=131) with T1a glottic cancer were recruited between January 2010 and September 2014. The included patients were randomly assigned to either receive CO2-LS (n=65) or LTP-RFA (n=66). We conducted the following multidimensional vocal assessments: (i) videostroboscopic evaluation; (ii) auditory-perceptual evaluation; (iii) aerodynamics/ efficiency; (iv) acoustics; and (v) self-assessment questionnaires. Meanwhile, the surgery time and three-year overall survival rates in two groups were recorded. The predefined primary endpoint was overall survival, and the minimum follow-up time was set to six months. RESULTS: After treatment, we found that the structure and vibration of vocal cord might recover more quickly in patients receiving LTP-RFA than in patients receiving CO2-LS, and moreover, the patients in the LTP-RFA group had the better vocal functions. Meanwhile, the surgery time was significantly less in the LTP-RFA group (8.83±1.59 minutes) than in the CO2-LS group (12.49±1.40 minutes) (p<0.00001). In addition, the two intervention methods had the similar three-year overall survival rates (94% versus 96%, p=0.58). CONCLUSION: These results indicated that both LTP-RFA and CO2-LS could effectively treat T1a glottic cancer, and LTP-RFA might have some advantages in voice function. Limited by the relatively small sample size, future studies were needed to validate our conclusion.

A Dynamic Rabbit Model of Sinus Barotrauma and Its Related Pathology.

BACKGROUND: This study was undertaken to establish a dynamic animal model of sinus barotrauma (SB). METHODS: The right nasal cavities of 65 rabbits were filled with sponges to obstruct the right ostiomeatal complex (OMC), while in the left nasal cavities, the left OMC was kept clear. The rabbits were exposed to hypobaric chamber simulation. The right sinuses were assigned as the model group, randomly divided into 13 subgroups with 5 in each subgroup, while the left sinuses were assigned as the control group. The hypobaric chamber simulation involved 6 pairs of ascending/descending speeds (100 m · s(-1), 75 m · s(-1), 50 m · s(-1)) to 2 altitudes (13,123 ft or 6562 ft). The ascending/descending speed for Model Group 13 was 15 m · s(-1) to an altitude of 13,123 ft. The control group was not exposed to hypobaric chamber simulation or obstruction of the OMC. All rabbits were monitored for behavior and via nasal endoscopy, MRI, and mucosal pathology, and statistically analyzed. RESULTS: SB appeared at the ascending/descending speeds of 50 m · s(-1), 75 m · s(-1), and 100 m · s(-1). SB was more obvious at 100 m · s(-1) than at 50 m · s(-1) and 75 m · s(-1), and SB happened mainly at altitudes between 0-6562 ft. Based on behavior during hypobaric chamber simulation and the results of endoscopic morphology, imaging, and cell pathology, SB could be divided into mild, moderate, and severe. DISCUSSION: By obstructing the OMC and using hypobaric chamber simulation at high ascending/descending speeds and altitude, a dynamic rabbit model of SB at various degrees was established. The severity of SB was proportional to the ascending/descending speeds and mainly seen below 6562 ft.

[Experimental studies for botulinum toxin type A to antagonist the VIP/PACAP expression on nasal mucosa in allergic rhinitis rat].

OBJECTIVE: To explore the expression and significance of vasoactive intestinal peptide and Pituitary adenylate cyclase activiting polypeptide (VIP/PACAP) of nasal mucosa in rats with allergic rhinitis (AR), and the function of botulinum toxin-A(BTX-A) to inhibit the expression of VIP/PACAP in AR. METHOD: Thirty Sprague-Dawley rats were randomly divided into 3 groups, which were the AR group, the intervention group, and the control group. In the AR group, ovalbumin was used to sensitize healthy rats. In the intervention group, BTX-A was dripped into the nasal cavity of AR rats 7 times. In the control group, only physiological saline was used to drip into the nasal cavity of AR rats. Changes of the rats' behavior were observed. ELISA were used to detected the concentration variation of serum IFN-γ and IL-4. Histopathology and immunohistochemistry were employed to observe morphology in the rats' nasal mucosal and the expression of VIP/PACAP. Statistical analysis was also made. RESULT: (1)The typical symptoms marks of nasal scratching, sneezing, nasal blockage and rhinorrhea of AR group (7.5 ± 0.50) were higher than intervention group (1 ± 0.27) and control group (0.8 ± 0.31). (2) Comparing to intervention group and control group, the serm IFN-γ of the AR group obvious reduced (P < 0.05), the serm IL-4 of the AR group obvious rose (P < 0.01), and the serm Th1/Th2 (IFN-γ/IL-4) of the AR group obvious reduced (P < 0.01). (3) Comparing to intervention group and control group, the cilium loss, inflammatory cells infiltration, and inflammatory cells exudation of nasal mucosa in AR group were more obviously (P < 0.01), and the intervention group of the 3 indexes was obviously than control group. (4) The expression of VIP in the rats' nasal mucosa of the AR group (13.27 ± 2.74) were more intense than intervention group (5.21 ± 2.18) and control group (3.56 ± 5.30) (P < 0.01), and the expression of PACAP in the rats' nasal mucosa of the AR group (20.97 ± 2.14) were more intense than intervention group (6.33 ± 3.04) and control group (4.63 ± 1.25) (P < 0.01). (5) In all the 3 groups, there was positive correlation between expression of negative in VIP/PACAP and Thl/Th2 cell infiltration(r were respectively -0.340 and -0.223, P < 0.05). CONCLUSION: The VIP/PACAP in the rats' nasal mucosa may play an important role in pathogenesis of AR, and BTX-A could improve the symptoms of AR through inhibition of the expression of VIP/ PACAP.

Natural IgM Switches the Function of Lipopolysaccharide-Activated Murine Bone Marrow-Derived Dendritic Cells to a Regulatory Dendritic Cell That Suppresses Innate Inflammation.

We have previously shown that polyclonal natural IgM protects mice from renal ischemia/reperfusion injury (IRI) by inhibiting the reperfusion inflammatory response. We hypothesized that a potential mechanism involved IgM modulation of dendritic cells (DC), as we observed high IgM binding to splenic DC. To test this hypothesis, we pretreated bone marrow-derived DC (BMDC) with polyclonal murine or human IgM prior to LPS activation and demonstrated that 0.5 × 10(6) IgM/LPS-pretreated BMDC, when injected into wild-type C57BL/6 mice 24 h before renal ischemia, protect mice from developing renal IRI. We show that this switching of LPS-activated BMDC to a regulatory phenotype requires modulation of BMDC function that is mediated by IgM binding to nonapoptotic BMDC receptors. Regulatory BMDC require IL-10 and programmed death 1 as well as downregulation of CD40 and p65 NF-κB phosphorylation to protect in renal IRI. Blocking the programmed death ligand 1 binding site just before i.v. injection of IgM/LPS-pretreated BMDC or using IL-10 knockout BMDC fails to induce protection. Similarly, IgM/LPS-pretreated BMDC are rendered nonprotective by increasing CD40 expression and phosphorylation of p65 NF-κB. How IgM/LPS regulatory BMDC suppress in vivo ischemia-induced innate inflammation remains to be determined. However, we show that suppression is dependent on other in vivo regulatory mechanisms in the host, that is, CD25(+) T cells, B cells, IL-10, and circulating IgM. There was no increase in Foxp3(+) regulatory T cells in the spleen either before or after renal IRI. Collectively, these findings show that natural IgM anti-leukocyte Abs can switch BMDC to a regulatory phenotype despite the presence of LPS that ordinarily induces BMDC maturation.