Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

The comparison of sensitivity of motion sickness between retinal degeneration fast mice and normal mice.

Recent studies report that a conflict between information from the visual system and vestibular system is one of the main reasons for induction of motion sickness (MS). We may be able to clarify the integration mechanism of visual and vestibular information using an animal model with a visual defect, the retinal degeneration fast (rdf) mouse, and the role of vestibular information in the pathogenesis of MS. The rdf mice and wild-type Kunming mice were subjected to rotary stimulation to induce MS. Conditioned taste anorexia to saccharin solution and behavior score were used to observe the differences in MS sensitivity between two types of mice. The decrease in intake of saccharin solution and the behavior score in rdf mice were greater than those in normal mice. After rotatory stimulation, the reduction of intake mass and the behavior score were greater in rdf mice compared to those of normal mice. The rdf mice were more sensitive to rotation than normal mice. We conclude that visual information plays a role in the pathogenesis of MS. Visual information and vestibular information impact each other and integrate through certain channels in the central nervous system in mice.

Nrg1/ErbB2 regulates differentiation and apoptosis of neural stem cells in the cochlear nucleus through PI3K/Akt pathway.

Sensorineural hearing loss (SNHL) is a common causes of disability. Neural stem cells (NSCs) from the cochlear nuclei have been considered to be a potential direction for the treatment of SNHL. Neuregulin 1 (NRG1)/ErbB2 signaling displays an essential role in nervous system development. In this study, we aimed to explore the roles of NRG1/ErbB2 in differentiation and apoptosis of cochlear nuclei NSCs. The data showed that the expression of NGR1 and ErbB2 in cochlear nuclei NSCs isolated from rats were increased with the age of rats. NRG1 treatment reduced the nestin-positive cells number, increased the MAP2-positive and GFAP-positive cells number, decreased the expression of cleaved-caspase-3, and increased the activation of PI3K/AKT. ErbB2 knockdown by lentiviral-mediated ErbB2 shRNA infection reversed the effect of NRG1 on cochlear nuclei NSCs. LY294002 administration further enhanced the effect of ErbB2 silencing on the expression of nestin, MAP2, GFAP and cleaved-caspase-3. Taken together, NRG1/ErbB2 regulates differentiation and apoptosis of cochlear nucleus NSCs through PI3K/Akt pathway.

Primary myxofibrosarcoma of the parotid: case report.

BACKGROUND: Myxofibrosarcoma is common in the extremities of elderly people and is characterized by a high frequency of local recurrence. CASE PRESENTATION: We report a 37 year old female who presented with a 4-month history of facial pain and a 3-month history of painful progressive swelling in the preauricular area. She underwent a total parotidectomy. The tumor was histopathologically and immunohistochemically diagnosed as a low-grade myxofibrosarcoma. The patient was free of disease 9 months after surgery with uneventful post-operative clinical course. CONCLUSIONS: Parotid area swelling should always alert doctors. To our knowledge, this is the first case of parotid myxofibrosarcoma. It should be added to the differential diagnosis of diseases of the parotid. We have to recognize this disease and seek adequate treatment for it.

Development and external validation of a nomogram to predict the risk of Upper gastrointestinal precancerous lesions in a non-high-incidence area.

BACKGROUND: Upper gastrointestinal precancerous lesions (UGPL) is the major preventable disease in non-high-incidence area. A prognostic nomogram was constructed to predict and identity susceptible population of UGPL before endoscope screening. METHODS: We recruited 300 ,016 eligible participants for upper gastrointestinal cancer (UGC) screening aged 40-74 years from two cities in Hunan province from 2012 to 2019. Individuals at high risk of UGC on basis of questionnaire estimation underwent endoscopic screening. Participants in two cities accepting endoscopy were used as training and external validation cohorts, respectively. A nomogram was developed based on independent prognostic factors of UGPL determined in multivariable logistic regression analysis. RESULTS: Of 35, 621 with high risk for UGC, 10, 364 subjects undertook endoscopy (participation rate of 29.1%). The detection rate for UGPL was 4.55%. The nomogram showed that age, gender, mental trama, picked food, and atrophic gastritis history in a descending order were significant contributors to UGPL risk. The C-index value of internal and external validation of the model is 0.612 and 0.670, respectively. The calibration data for UGPL showed optimal agreement between the nomogram prediction and actual observation. Furthermore, high-risk and low-risk group divided based on score from the nomogram predicted a significantly distinct detection rate. CONCLUSION: The nomogram provides screening workers a simple and accurate tool for identifying individuals at a higher risk of UGPL as primary screening before endoscopy among Chinese population in non-high-risk areas, thus reducing the incidence of UGC by improving the UGPL detection.

[Immunogenicity of multi-epitopes gene of major outer membrane protein of Chlamydia trachomatis].

OBJECTIVE: To construct a recombinant eukaryotic expression plasmid pcDNA3.1-Ct MOMP168 including Ct MOMP multi-epitopes gene, and evaluate the Ct MOMP-specific humoral and cellular immune response induced by pcDNA3.1-Ct MOMP168 in BALB/c mice. METHODS: Recombinant plasmid pcDNA3.1-Ct MOMP168 including Ct MOMP multi-epitopes gene was constructed. Then, BALB/c mice were randomly assigned to receive (intramuscular injection) either pcDNA3.1-Ct MOMP168 or pcDNA3.1 or PBS (n = 12, 100 microg/time per mouse), and the same immunization schedule was repeated for the third time at 2 week intervals. The titers of anti-Ct MOMP antibody and its antibody subtypes in sera, the cytotoxicity of Ct MOMP-specific cytotoxic T lymphocyte (CTL) in spleen, and the level of cytokine (IFN-gamma, IL-4, IL-10)-producing CD3(+) T cells in spleen were detected by ELISA, LDH release assays and intracellular cytokine staining-fluorescence activated cell sorter (ICS-FACS), respectively. RESULTS: The recombinant plasmid pcDNA3.1-Ct MOMP168 was able to induce Ct-specific antibody response (A(490) = 0.973 +/- 0.136; serum titer was 1:1000) as compared with pcDNA3.1 (A(490) = 0.180 +/- 0.025) and PBS (A(490) = 0.110 +/- 0.015), and the major antibody subtype was IgG2a with statistical significance (F = 106.884, P < 0.05). When the ratio of effector cells and target cells reached to 50:1, the activity of cytotoxic T-lymphocyte in pcDNA3.1-Ct MOMP168 immunized mice (41.71% +/- 8.34%) was significantly higher (F = 22.315, P < 0.05) than that in pcDNA3.1 immunized mice (18.40% +/- 3.45%) and PBS immunized mice (14.50% +/- 2.42%). The levels of CD3(+) IFN-gamma(+) T cells in pcDNA3.1-Ct MOMP168 immunized mice (1.15% +/- 0.16%) were significantly higher (F = 99.638, P < 0.05) than that in pcDNA3.1 immunized mice (0.12% +/- 0.08%) and PBS immunized mice (0.09% +/- 0.03%), while the significant difference in the levels of IL-4(+) CD3(+) T cells and IL-10(+) CD3(+) T cells was not observed (F = 0.886 and 1.112, P > 0.05) between pcDNA3.1-Ct MOMP168 immunized mice (0.13% +/- 0.08% and 0.14% +/- 0.08%) and pcDNA3.1 (0.07% +/- 0.05% and 0.13% +/- 0.06%) or PBS immunized mice (0.08% +/- 0.04% and 0.07% +/- 0.04%). CONCLUSION: In BALB/c mice, the recombinant plasmid pcDNA3.1-Ct MOMP168 might induce not only the generation of Ct-specific antibody, but also the high level of Ct MOMP-specific CD3(+) IFN-gamma(+) T cells.

[An effective combined therapy for simple premature ejaculation].

OBJECTIVE: To observe the clinical effect of a combined therapy in the treatment of simple premature ejaculation. METHODS: A total number of 110 patients with simple premature ejaculation were divided into a control group (n = 50), given oral hydrochloric acid sertraline only, and a combined therapy group (n = 60), treated by oral administration of hydrochloric acid sertraline, local inunction of a traditional Chinese medicine and guidance in sexual psychology and knowledge. At the end of a 4-week treatment and 4 weeks after the drug withdrawal, the therapeutic effects were evaluated by ejaculation latency and satisfaction with sexual life. RESULTS: The total effectiveness rates at the end of the 4-week treatment were 91.6% and 76% in the combined therapy and the control groups, while those 4 weeks after the drug withdrawal were 68.3% and 42% respectively, both with significant differences in between (P < 0.05 and P < 0.01). CONCLUSION: The combined therapy has a satisfactory clinical effect and stability in the treatment of simple premature ejaculation.

Development of self-microemulsifying drug delivery systems for oral bioavailability enhancement of alpha-Asarone in beagle dogs.

A self-microemulsifying drug delivery system (SMEDDS) for enhancement of oral absorption of a poor water-soluble drug, alpha-Asarone (ARE), is reported. Solubility of ARE was determined in various vehicles. SMEDDS consisted of a mixture of oils, surfactants, and cosurfactants that were emulsified in an aqueous medium under the gentle agitation and digestive motility. Pseudo-ternary phase diagrams were used to identify the efficient self-emulsification regions. The particle size distribution of the resulting microemulsions was determined using a laser scatter particle size analyzer (LSPSA). The optimized SMEDDS formulations containing Ethyl oleate (20%), Tween 80 (60%), and PEG 400 (20%) were tested for in vitro dissolution. The percentage of ARE released from the SMEDDS was significantly higher than that from the conventional tablets. Oral bioavailability of ARE in the SMEDDS via the hard capsules and the conventional tablets was evaluated in fasted beagle dogs. The bioavailability of ARE formulated in SMEDDS showed approximately 4.8-fold higher bioavailability than that in the conventional tablets. The results indicated that SMEDDS is potentially a good drug delivery system for oral delivery of the hydrophobic compound ARE.

MicroRNA-485-5p suppresses cell proliferation and invasion in hepatocellular carcinoma by targeting stanniocalcin 2.

Increasing evidences indicate that dys-regulation of MicroRNAs contributes to hepatocellular carcinoma. However, the roles of miR-485-5p in HCC are still largely unexplored. In the present study, our quantitative real-time PCR analysis found that miR-485-5p was significantly down-regulated in 50 pairs of human HCC tissues. Moreover, the reduced expression of miR-485-5p was significantly correlated with larger tumor size and more tumor number in patients with HCC. In vitro studies further showed that overexpression of miR-485-5p mimics could inhibit, while its antisense oligos promote cell proliferation and invasion. Results from the dual-luciferase reporter gene assays and western blot further showed that stanniocalcin 2 was a direct target of miR-485-5p. Therefore, our data suggest a novel role for miR-485-5p in the regulation of HCC progression.

Anticancer drug resistance of HeLa cells transfected with rat glutathione S-transferase pi gene.

OBJECTIVE: To establish a cytologic expressing system of rat glutathione S-transferase pi (GST-pi) cDNA for detecting the resistance of HeLa cells to anticancer drugs. METHODS: The assessment was made with various anticancer drugs (adriamycin, mitomycin, cisplatinum and vincristine) that showed different cytotoxicities in transfectant HeLa cells with pSV-GT containing rat GST-pi cDNA (HeLa/pSV-GT) or control pSV-neo (HeLa/pSV-neo). Expression levels of GST-pi mRNA in HeLa/pSV-GT and HeLa/pSV-neo were measured by in situ hybridization using Digoxin-labelled cDNA probe. RESULTS: HeLa/pSV-GT expressed significantly high degree of GST-pi mRNA, whereas both HeLa/pSV-neo and HeLa cells had very low expression. Cytotoxicities of HeLa/pSV-GT and HeLa/pSV-neo with 4 anticancer drugs were measured by MTT assay. Drug concentrations for yielding 50% inhibition (IC50) in HeLa/pSV-GT by adriamycin, mitomycin and cisplatinum were 70.13 microg/mL, 10.95 microg/mL and 16.52 microg/mL, respectively. In contrast, IC50 in HeLa/pSV-neo was 10.34 microg/mL, 7.48 microg/mL and 13.70 microg/mL, respectively. The cytotoxicities of vincristine on both HeLa/pSV-GT and HeLa/pSV-neo were not significantly different. CONCLUSIONS: Our findings suggest that HeLa/pSV-GT containing rat GST-pi cDNA is resistant to some anticancer drugs due to overexpression of GST-pi. Also, HeLa/pSV-GT cell line could serve as a useful cytogenetic model for further research.

Publications about hearing in otorhinolaryngology journals from chinese authors: a 11-year survey of the literature.

Hearing loss is a leading cause of disability in China. However, the research status in the field of hearing among Chinese individuals in the three major regions of China: Mainland (ML), Hong Kong (HK) and Taiwan (TW), are unknown. The output of hearing articles published in international otorhinolaryngology journals from these three regions were compared in this study. Articles published in 31 international otorhinolaryngology journals related to hearing originating from the ML, TW and HK from 2000 to 2011 were retrieved from the PubMed database search. The number of total articles, clinical trials, randomized controlled trials, case reports, and articles published in the top 5 international otorhinolaryngology journals were assessed in terms of quantity and quality comparisons. The total number of articles from the three regions increased significantly from 2000 to 2011. There were 379 articles from ML (143), TW (180) and HK (56) in the past 10 years. The number of articles published per year from the ML has exceeded those from TW in 2009 and HK in 2003. TW had the most articles (46) published in the top 5 international otorhinolaryngology journals among the three regions. The total number of articles from the three major regions of China increased significantly from 2000 to 2011. The numbers of articles published per year from the ML have exceeded those from TW and HK. However, the quality of articles from TW is better than that from ML.

Determining leak locations during transnasal endoscopic repair of cerebrospinal fluid rhinorrhea.

OBJECTIVE: For transnasal endoscopic repair procedures to be successful, it is critical to identify leak locations during surgery. We aim to evaluate different methods to more accurately detect leak locations during the endoscopic repair of cerebrospinal fluid rhinorrhea. MATERIALS AND METHODS: We performed a retrospective chart review of 39 cases undergoing endoscopic repair of cerebrospinal fluid rhinorrhea. The leak locations were determined using preoperative nasal endoscopy, radioisotope scanning, the intraoperative image-guided system, and intraspinal normal saline injection. RESULTS: The cerebrospinal fluid leak location was in the sphenoidal sinus in 9 cases, the ethmoid sinus in 17 cases, and in the frontal sinus in 1 case. The leak locations could not be determined in the remaining 12 cases using this method alone. For these 12 cases, after the ethmoid sinus was opened and the lateral wall of sphenoidal sinus was exposed with the aid of the intraoperative image-guided system, outflow of cerebrospinal fluid was present on the lateral wall of sphenoidal sinus (in 1 case) and on the ethmoid roof (in 3 cases). Furthermore, using intraspinal saline injection (20-30 ml), leak locations were detected in the sphenoidal sinus (2 cases) and in ethmoid sinus (6 cases) of the remaining cases. CONCLUSION: For cerebrospinal fluid rhinorrhea patients whose leak locations are difficult to determine, surgeons can increase their operative success rates by performing radioisotope scanning and intraspinal saline injections and by using image-guided surgical systems. These safe and effective methods can be used to successfully detect leak locations during transnasal endoscopic repair of cerebrospinal fluid leaks.