[Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population].

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

[Deep neck space infections: a retrospective cohort study of surgical risk factors].

Objective: To explore risk factors affecting treatment for deep neck space infections (DNSIs) so as to provide guidance for appropriate early managements. Methods: A retrospective cohort study was conducted on inpatients with DNSIs admitted to the Department of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Qingdao University from March 2013 to February 2021. Patients were divided into surgical and non-surgical groups based on whether they had surgery or not. Information collected included demographic data, disease-related signs and symptoms, treatment history, systemic comorbidities, imaging data and laboratory indicators. Hypothesis testing, univariate Logistic regression and multivariate Logistic regression were used for data processing. Resuts A total of 61 patients were included, including 37 males and 24 females, aged 6-96 years. There were 35 cases (57.4%) in the surgical group and 26 cases (42.6%) in the non-surgical group. Multivariate analysis showed that risk factors for surgery as followings: neck dyskinesia (OR=0.03, 95%CI: 0.00-0.24), dysphagia (OR=0.10, 95%CI: 0.02-0.72), serum white blood cell count≥16.74×109/L (OR=1.18, 95%CI: 1.01-1.39) and interspace gas (OR=0.03, 95%CI: 0.00-0.30). Conclusion: Clinicians should be alert to these risk factors for surgery in the course of treatment and timely surgical treatment for patients who meet the conditions.

Essential signals in publication trends and collaboration patterns in global Research Integrity and Research Ethics (RIRE).

Amid an increasingly demanding research environment, there has been a growing interest in studies concerning Research Integrity and Research Ethics (RIRE). Between 1990 and 2020, over 9700 publications were published to address problematic research conduct such as falsification, plagiarism, and related protocols and standards. In this work, country-level trends and collaborative structures are examined with respect to economic group. Our results showed that RIRE publications are predominantly led by the West, with North America and Western Europe contributing the most. While there is interest within growing economies such as China, the pace is not comparable to its overall publications. However, international collaborations on RIRE grew to account for nearly 30% of all publications on the subject in 2020. Although there is a stronger preference for high income countries to collaborate with other high income countries, we observe a rise in partnerships between high-/middle-income and middle-/lower-income co-authorship pairs in the last decade. These trends point to a maturing global community with distributed knowledge transfer, towards more unified international standards for research ethics and integrity. Supplementary Information: The online version contains supplementary material available at 10.1007/s11192-022-04400-y.

[Transoral endoscopic resection of benign tumors in parapharyngeal space via medial pterygomandibular raphe approach].

Objective: To explore the surgical methods and effects of transoral endoscopic resection of benign tumors in parapharyngeal space via medial pterygomandibular raphe approach. Methods: The clinical data of 23 patients who underwent resection of benign tumors in parapharyngeal space by endoscopic medial pterygomandibular raphe approach from January 2016 to July 2020 in the Department of Otorhinolaryngology Head and Neck Surgery, the Affiliated Hospital of Qingdao University were analyzed retrospectively. There were 14 males and 9 females with a median age of 43 years. The tumors were located in the anterior space of the styloid process in 13 cases and in the posterior space in 10 cases. The smallest tumor volume was 7.3 ml and the largest was 80.2 ml. The preoperative imaging features, the characteristics and risks of this approach in the operation were analyzed, and the feasible mode of operation was explored. Results: All patients completed the operation successfully. The intraoperative blood loss was 20 to 50 ml, with an average of 28.3 ml. The operation time was 40 to 110 min, with an average of 75.4 min. The incision length was 2 to 4 cm, with an average of 3.0 cm. The postoperative pain score was 2 to 4, with an average of 3.2. The postoperative hospital stay was 4 to 9 d, with an average of 6.7 d. Postoperative pathological diagnosis included pleomorphic adenoma (n=12), neurilemmoma (n=10) and basal cell adenoma (n=1). The patients were followed up for 6 to 60 months. There was no postoperative complication such as infection or serious bleeding, and there was no tumor recurrence after operation. Conclusion: Endoscopic resection of benign tumor in parapharyngeal space via medial pterygomandibular raphe approach is a safe, effective, and minimally invasive surgical method for the treatment of tumors in parapharyngeal space.

[Application of endoscopic resection of benign tumor in infratemporal fossa].

Objective: To explore the application of endoscopy and clinical effect of endoscopic resection of benign tumor in infratemporal fossa. Methods: The clinical data of 11 patients with benign tumors in infratemporal fossa admitted to the Department of Otorhinolaryngology Head and Neck Surgery and Skull Base Surgery of the Affiliated Hospital of Qingdao University from January 2016 to September 2018 were retrospectively analyzed. There were 6 males and 5 females, with the age ranging from 11 to 63 years old. The main clinical manifestations were pharyngeal foreign body sensation, submaxillary pain, maxillofacial numbness and tongue numbness. Imaging examination showed that the tumor was round and had a clear boundary with the surrounding tissue. All the patients underwent endoscopic surgery. Appropriate surgical approach was selected according to the location of the tumor and its relationship with the internal carotid artery. The endoscopic surgical approaches included trans-oropharyngeal approach in 7 cases, trans-lateral pterygomandibular raphe approach in 1 case and trans-medial pterygomandibular raphe approach in 3 cases. The pathological results, prognosis, complications and relapse of patients were summarized through descriptive statistics. Results: The tumors were completely resected under endoscope in all patients, and there was no significant complication occurred after surgery. The average pain VAS score was 3.1 after surgery and average hospital stay was 5.9 d. The postoperative pathological diagnoses consisted of 6 cases of pleomorphic adenoma, 4 cases of neurilemmoma and 1 case of basal cell adenoma. All patients were followed up regularly from 6 to 39 months without recurrence of tumor. Conclusion: Endoscopic resection of benign tumors in infratemporal fossa has the advantages of minimal damage, rapid recovery, few complications, and definite curative effect, which can be used as an important alternative for surgical treatment of benign tumors.

[Analysis of clinical features of respiratory epithelial adenomatoid hamartoma in the nasal cavity].

Objective: To analyze the clinical features of respiratory epithelial adenomatoid hamartoma (REAH) in the nasal cavity. Methods: Clinical datas of 23 patients, who were hospitalized in Department of Otorhinolaryngology Head and Neck Surgery, the Affiliated Hospital of Qingdao University, from February 2016 to February 2018 with histopathologically proved REAH in the nasal cavity were reviewed. There were 18 males and 5 females, with the age range from 16 to 71 years old. The most common area, main symptoms, surgical methods and follow-up results were analyzed. Results: The most common area was olfactory cleft (21 cases), and the mainly symptom was nasal congestion (18 cases). All the patients received transnasal endoscopic surgery and had no recurrence during following-up from three months to one year. Conclusions: The most common area of REAH in the nasal cavity is the olfactory cleft. Histopathological result is needed to make a definite diagnosis. Complete surgical resection is the main treatment.

[Clinical analysis of transnasal endoscopic repair of cerebrospinal fluid rhinorrhea].

Objective:To summarize the common clinical types of cerebrospinal fluid（CSF） rhinorrhea and key points of transnasal endoscopic repair of CSF rhinorrhea. To evaluate clinical effects. Method:In 29 patients with cerebrospinal fluid rhinorrhea, 9 patients with traumatic CSF rhinorrhea, 10 patients with spontaneous CSF rhinorrhea, 7 patients with CSF rhinorrhea after tumour excision, and 3 patients with iatrogenic CSF rhinorrhea. All the 29 patients were treated with transnasal endoscopic repair of CSF rhinorrhea. Result:There were 25 patients were successfully repaired at one time. Three patients developed intracranial infection and 2 patient developed pneumocephalus after surgery, all of them were cured with conservative treatment. All the patients who were followed-up for more than half a year had no recurrence. Conclusion:Transnasal endoscopic repair of CSF rhinorrhea is safe and effective, the success rate of operation is high, it is not easy to recur, and the complications are few. It can be used as the first choice for repairing of CSF rhinorrhea and effective prevention measures. Accurate location of leak, appropriate repair, effective reconstruction of the skull base, continuous drainage of the lumbar cistern when necessary and active prevention of intracranial infection are critical to the success of operation.

[Clinical analysis of orbital complications due to rhinosinusitis in 28 cases].

Objective: To investigate the clinical characteristics of orbital complications due to rhinosinusitis and to provide the basis for the diagnosis and treatment of this disease. Methods: Retrospectively analyzed the clinical data of 28 patients with orbital complications due to rhinosinusitis who were admitted into the Affiliated Hospital of Qingdao University, Department of Otorhinolaryngology from August 2009 to April 2017. In all 28 cases, there were 1 case with preseptal cellulites, 9 cases with orbital cellulites, 13 cases with subperiosteal orbital abscess and 5 cases with orbital abscess. Among all the patients, 9 were younger than 14. Two patients were in ages from 14 to 17 and 7 patients were at or above 18 years. Absolute medicine therapy was performed on 8 patients and combined therapy of operation and pharmacotherapy on 20 patients. Results: The patients were followed up for 2 to 19 months. Both the general symptoms and ocular symptoms disappeared and nasal ventilation function recovered well. Conclusions: The treatment for orbital complications of rhinosinusitis includes absolute medicine therapy and combined therapy of operation and pharmacotherapy. And the selection of treatment depends on disease stage. Timely diagnosis and reasonable treatment would be beneficial in the recovery of patients.

Influence of international co-authorship on the research citation impact of young universities.

We investigated the effect of international collaboration (in the form of international co-authorship) on the impact of publications of young universities (<50 years old), and compared to that of renowned old universities (>100 years old). The following impact indicators are used in this study, they are: (1) the 5-year citations per paper (CPP) data, (2) the international co-authorship rate, (3) the CPP differential between publications with and without international co-authorships, and (4) the difference between the percentage of international co-authored publications falling in the global top 10 % highly cited publications and the percentage of overall publications falling in the global top 10 % highly cited publications (Δ%Top10%). The increment of 5-year (2010-2014) field weighted citation impact (FWCI) of internationally co-authored papers over the 5-year overall FWCI of the institutions in SciVal® is used as another indicator to eliminate the effect of discipline difference in citation rate. The results show that, for most top institutions, the difference between the citations per paper (CPP) for their publications with and without international co-authorship is positive, with increase of up to 5.0 citations per paper over the period 1996-2003. Yet, for some Asian institutions, by attracting a lot of researchers with international background and making these collaborating "external" authors as internal researchers, these institutions have created a special kind of international collaboration that are not expressed in co-authorship, and the CPP gaps between publications with and without international co-authorship are relatively small (around 0-1 citations per paper increment) for these institutions. The top old institutions have higher CPP than young institutions, and higher annual research expenditures; while young universities have a higher relative CPP increment for the current 5-year period over the previous 5-year period. The Δ%Top10% for international co-authored publications is generally higher than that for all journal publications of the same institution. With the increase of international co-authorship ratio, the mean geographical collaboration distance (MGCD, an indication of increased international co-authorship) of one institution based on the Leiden Ranking data also increases, and young institutions have relatively higher CPP increment over MGCD increment. International co-authorship has a positive contribution to the FWCI of the institution, yet there are untapped potential to enhance the collaboration among young institutions.

[The impacts of endoscopic sinus surgery with middle turbinate and superior turbinate resection on quality of life and olfactory function in patients with chronic rhinosinusitis with nasal polyps].

Objective:The aim of this study is to investigate the impacts of endoscopic sinus surgery(ESS) with middle turbinate and superior turbinate resection on quality of life and olfactory function in patients with chronic rhinosinusitis with nasal polyps(CRSwNP) and with dysosmia. Method:All of the 81 patients with CRSwNP and with dysosmia recieved ESS with middle turbinate and superior turbinate resection.The patients were given standardized drug treatments during the preoperative period,such as nasal irrigation,using local hormone spray,mucus decorporation agent by oral,using macrolide antibiotics according to the circumstances and so on.We used SNOT-20 to evaluate the quality of life preoperatively and postoperatively in patients;and used the T&T olfactory testing and VAS to evaluate the olfactory function of the patients.Result:The SNOT-20 test showed that "need to blow nose", "lack of a good sleep", "thick nasal discharge", "difficult to go to sleep",and "awkward" influence on the quality of life severely.The scores of all items showed decreasing tread in 2 weeks,1 month and 3 months after operation(P <0.05).Olfactory:Among the 81 patients(162 side),54 patients(108 sides) lost sense of smell completely in preoperative period and 27 patients' olfaction lost in varying degrees(10 patients are bilateral symmetry hyposmia and 17 patients are bilateral asymmetry hyposmia).Compared with the preoperative period,70 patients'(86.4%) olfactory function were improved at 3 months after the operation,in which 43 patients'(53.1%) olfactory function recovered to normal,and 27 patients'(33.3%) olfactory function improved in varying degrees;however,11 patients'(13.6%) olfactory function had not improvement at all.Sixty-one patients were followed up for more than one year.One year after operation,53 patients'(86.9%) olfactory function were improved,in which the 31 patients' (50.8%) olfactory function recovered to normal and 22 patients'(36.1%)olfactory function improved in varying degrees;8 patients'(13.1%) olfactory function had no improvement;the remaining 20 patients are being followed up.There was a significant difference between preoperative T&T olfactory testing and postoperative's(P <0.05);and so was VAS assessment(P <0.05). Conclusion: For the patients with CRSwNP and with dysosmia,the operation of ESS with middle turbinate and superior turbinate resection combined with standardized drug treatment in preoperative period can effectively improve the patients' quality of life and olfactory function.Hyperventilation and nasal dryness caused by excessive resection were not found.

MUC1 extracellular domain confers resistance of epithelial cancer cells to anoikis.

Anoikis, a special apoptotic process occurring in response to loss of cell adhesion to the extracellular matrix, is a fundamental surveillance process for maintaining tissue homeostasis. Resistance to anoikis characterises cancer cells and is a pre-requisite for metastasis. This study shows that overexpression of the transmembrane mucin protein MUC1 prevents initiation of anoikis in epithelial cancer cells in response to loss of adhesion. We show that this effect is largely attributed to the elongated and heavily glycosylated extracellular domain of MUC1 that protrudes high above the cell membrane and hence prevents activation of the cell surface anoikis-initiating molecules such as integrins and death receptors by providing them a mechanically 'homing' microenvironment. As overexpression of MUC1 is a common feature of epithelial cancers and as resistance to anoikis is a hallmark of both oncogenic epithelial-mesenchymal transition and metastasis, MUC1-mediated cell resistance to anoikis may represent one of the fundamental regulatory mechanisms in tumourigenesis and metastasis.

Circulating galectins -2, -4 and -8 in cancer patients make important contributions to the increased circulation of several cytokines and chemokines that promote angiogenesis and metastasis.

BACKGROUND: Circulating concentrations of the cytokines interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) and chemokines monocyte chemotatic protein 1 (MCP-1)/CCL2 and growth-regulator oncogene α (GROα)/chemokine C-X-C motif ligand 1 are commonly increased in cancer patients and they are increasingly recognised as important promoters, via divergent mechanisms, of cancer progression and metastasis. METHODS: The effect of galectins-2, -4 and -8, whose circulating levels are highly increased in cancer patients, on endothelial secretion of cytokines was assessed in vitro by cytokine array and in mice. The relationship between serum levels of galectins and cytokines was analysed in colon and breast cancer patients. RESULTS: Galectins-2, -4 and -8 at pathological concentrations induce secretion of G-CSF, IL-6, MCP-1 and GROα from the blood vascular endothelial cells in vitro and in mice. Multiple regression analysis indicates that increased circulation of these galectins accounts for 41∼83% of the variance of these cytokines in the sera of colon and breast cancer patients. The galectin-induced secretion of these cytokines/chemokines is shown to enhance the expression of endothelial cell surface adhesion molecules, causing increased cancer-endothelial adhesion and increased endothelial tubule formation. CONCLUSION: The increased circulation of galectins -2, -4 and -8 in cancer patients contributes substantially to the increased circulation of G-CSF, IL-6 and MCP-1 by interaction with the blood vascular endothelium. These cytokines and chemokines in turn enhance endothelial cell activities in angiogenesis and metastasis.

Characterization of spark plasma sintered Ag nanopowders.

The low temperature sintering behaviour of nanocrystalline Ag powder (with an average size of 70 nm) was characterized. Using spark plasma sintering (SPS), the Ag nanopowders can be successfully sintered at low pressure for only 5 min without external heating, and the sintering density increases and porosity decreases significantly with increase in the sintering temperature. Nanoindentation has been used to characterize the SPS sintered Ag samples. The mechanisms of the low sintering temperature behaviour of the nano-Ag powder and the nanoscale mechanical performance have been discussed. Compression tests were also used to characterize the mechanical properties of the sintered Ag sample with a maximum strain up to 15%.

Plagiochin E, a botanic-derived phenolic compound, reverses fungal resistance to fluconazole relating to the efflux pump.

AIM: In this study, we investigated the effect of plagiochin E (PLE), a botanic-derived phenolic natural product, on reversal of fungal resistance to fluconazole (FLC) in vitro and the related mechanism. METHODS AND RESULTS: A synergistic action of PLE and FLC was observed in the FLC-resistant Candida albicans strains and was evaluated using the fractional inhibited concentration index. The effect of PLE on FLC intracellular uptake was investigated in FLC-resistant C. albicans cells by liquid chromatography-tandem mass spectrometry, and the effect on efflux drug pump was assessed by measuring the efflux of Rhodamine 123 (Rh123). PLE significantly inhibited the efflux, but not the absorption, of Rh123 in FLC-resistant strains in phosphate-buffered saline with 5% glucose. Overexpression of the multidrug-resistance gene CDR1 in FLC-resistant C. albicans isolates was detected, and the introduction of PLE to the cells showed a significant reduction of the CDR1 expression in those FLC-resistant isolates. CONCLUSIONS: These findings indicate that PLE could reverse the fungal resistant to FLC by inhibiting the efflux of FLC from C. albicans, and this effect may be related to the efflux pump. SIGNIFICANCE AND IMPACT OF THE STUDY: These results indicate that the combination of PLE and FLC may provide an approach for the clinical therapy of fungus infection induced by FLC-resistant strains.

Effect of spark plasma sintering on the microstructure and in vitro behavior of plasma sprayed HA coatings.

The crystalline phases and degree of crystallinity in plasma sprayed calcium phosphate coatings on Ti substrates are crucial factors that influence the biological interactions of the materials in vivo. In this study, plasma sprayed hydroxyapatite (HA) coatings underwent post-spray treatment by the spark plasma sintering (SPS) technique at 500 degrees C, 600 degrees C, and 700 degrees C for duration of 5 and 30 min. The activity of the HA coatings before and after SPS are evaluated in vitro in a simulated body fluid. The surface microstructure, crystallinity, and phase composition of each coating is characterized by scanning electron microscopy and X-ray diffractometry before, and after in vitro incubation. Results show that the plasma sprayed coatings treated for 5 min in SPS demonstrated increased proportion of beta-TCP phase with a preferred-orientation in the (214) plane, and the content of beta-TCP phase corresponded to SPS temperature, up to 700 degrees C. SPS treatment at 700 degrees C for 30 min enhanced the HA content in the plasma spray coating as well. The HA coatings treated in SPS for 5 min revealed rapid surface morphological changes during in vitro incubation (up to 12 days), indicating that the surface activity is enhanced by the SPS treatment. The thickest apatite layer was found in the coating treated by SPS at 700 degrees C for 5 min.

Interaction between bacterial peptides, neutrophils and goblet cells: a possible mechanism for neutrophil recruitment and goblet cell depletion in colitis.

Goblet cell depletion occurs in various forms of colitis, but its mechanism is unknown. We have investigated two linked hypotheses: (i) that bacterial peptides, such as formyl-methionyl-leucyl-phenylalanine (fMLP), interact with epithelial cells inducing the release of chemokines, including interleukin-8 (IL-8), which in turn leads to the recruitment of neutrophils which release mucin secretagogues; (ii) that fMLP acts directly on epithelial cells to cause mucus secretion. Studies were performed to measure the effects of fMLP on the synthesis and secretion of IL-8 and mucus by the goblet cell differentiated colon cancer cell lines HT29-MTX (methotrexate-conditioned HT29 colonic adenocarcinoma cell line) and LS174T, and to assess the effects of neutrophil-derived secretagogues on goblet cell secretion in these cell lines. fMLP (0.1 microM) increased the secretion of IL-8 by 105% (P<0.0001) in HT29-MTX cells and by 401% (P<0.0001) in LS174T cells. fMLP also increased the synthesis and secretion of mucins by these cell lines, with maximal effects of 65% above control values for synthesis (P<0.01) and 73% for secretion (P<0.01). A dose-related increase (up to 67%; P<0.01) in mucin secretion was demonstrated in HT29-MTX cells in response to incubation with supernatant from activated neutrophils. This effect was largely (83%; P<0.02) inhibited by ICI 200,355, a specific inhibitor of neutrophil elastase. In conclusion, the bacterial peptide fMLP and neutrophil elastase are both potent mucus secretagogues for colon epithelial cells. fMLP also elicits release of the potent neutrophil chemoattractant IL-8 from colon epithelial cells. These findings support the hypothesis that the mucosal inflammation and mucus depletion seen in ulcerative colitis could result from interaction between bacterial peptides and the mucosa.

Expression of Schwann cell-specific proteins and low-molecular-weight neurofilament protein during regeneration of sciatic nerve treated with neurotrophin-4.

Neurotrophin-4 acts as a potent survival factor for subpopulations of motoneurons. To investigate its effect on Schwann cell sheath and axonal proteins during peripheral nerve regeneration, sciatic nerves in adult rats were transected and repaired, and fibrin glue containing neurotrophin-4 injected around the repair site. At 5, 15, 30 and 60 days after repair, 5-mm nerve segments distal to the repair were collected, and western blotting was used to measure myelin-associated glycoprotein, myelin basic protein and low-molecular-weight neurofilament protein. In control groups these dramatically declined at 5 and 15 days then increased from 30 and 60 days. However, in the neurotrophin-4 group there was a significant increase (to several times basal values) in myelin-associated glycoprotein and myelin basic protein at 5-15 days. The relatively small increases (<7%) in Schwann cell numbers suggest that this is mainly due to increased synthesis per cell. The neurotrophin-4 group also showed a small but significant increase at 15 days in low-molecular-weight neurofilament protein, which however remained much lower than basal. We conclude that neurotrophin-4 regulates the expression of myelin-associated glycoprotein, myelin basic protein, and to a lesser extent low-molecular-weight neurofilament protein, during peripheral nerve regeneration.