Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

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.

Patterns of Caudate Lobe Invasion of Hilar Cholangiocarcinoma: A Panoramic Histologic Study of Liver.

BACKGROUND: At present, caudate lobectomy (CL) in hilar cholangiocarcinoma (HCCA) was controversial. Our study was designed to investigate the features of caudate lobe invasion (CLI) by whole-mount histologic large sections (WHLS). METHODS: A total of 46 HCCA patients underwent hemihepatectomy or trisectionectomy combined with CL were included. Serial WHLS (120 mm × 100 mm) were collected, and the relationship between caudate lobe and tumor was retained to determine the incidence of CLI. Hematoxylin and eosin (HE) and immunohistochemical (IHC) staining were completed to further explore the pathway of CLI. RESULTS: The whole region of the Glisson system in caudate lobe and hilar area can be clearly displayed by WHLS, and 32 (32/46 69.6%) patients were identified with CLI. There were three different pathways of CLI with panoramic IHC staining. The most common pathway is through the fibrous connective tissue along Glisson system (20/32 62.5%, without carcinoma in bile ducts). The Bismuth type, tumor size, vascular invasion, pathological type, and hepatic invasion were related to the CLI (p < 0.05). CONCLUSIONS: The incidence and distribution of CLI provided histologic evidence for CL in HCCA. Based on the invasion pathway, it is necessary to assess the fibrous connective tissue in Glisson system of caudate lobe in pathological research and practice.

Characteristic of Perineural Invasion in Hilar Cholangiocarcinoma Based on Whole-Mount Histologic Large Sections of Liver.

Background & Objective: Perineural invasion is an important biological feature of hilar cholangiocarcinoma (HCCA). We developed a whole-mount histologic large sections (WHLS) of the liver to evaluate peripheral nerve invasion (PNI) of HCCA. Methods: Using sampling, fixation, dehydration, embedding, sectioning, hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining, and scanning, the characteristics of intrahepatic and extrahepatic PNI in 20 patients with Bismuth type III and type IV HCCA were analyzed with WHLS. Correlation between the characteristics of nerve invasion and tumor size, vascular invasion (artery, portal vein), degree of differentiation, microvascular invasion (MVI), carbohydrate antigen19-9 (CA19-9), and differentiation degree of HCCA was statistically evaluated. Results: The WHLS of the liver was successfully established, which enabled us to observe intrahepatic and extrahepatic distribution of HCCA and whether surrounding tissues including nervous, blood, and lymph vessels were infiltrated. Extrahepatic and intrahepatic PNI were identified in 20 (100%) patients and 1 (5.0%) patient, respectively. Vessel density decreased in most invaded nerves presented by CD-34, which correlated with 100% of poorly differentiated and 83% of moderately differentiated tumors (P<0.008). Conclusion: This study established a WHLS of the liver that can be used for clinical diagnosis and research, and confirmed that extrahepatic PNI is prevalent, but intrahepatic nerve invasion is rare and does not accompany the invasion scope of bile ducts in types III and IV HCCA. In addition, moderately and poorly differentiated malignant tumors are more prone to PNI, independent of blood supply.

Extrahepatic bile duct reconstruction in pigs with heterogenous animal-derived artificial bile ducts: A preliminary experience.

BACKGROUND: Extrahepatic biliary duct injury (BDI) remains a complicated issue for surgeons. Although several approaches have been explored to address this problem, the high incidence of complications affects postoperative recovery. As a nonimmunogenic scaffold, an animal-derived artificial bile duct (ada-BD) could replace the defect, providing good physiological conditions for the regeneration of autologous bile duct structures without changing the original anatomical and physiologic conditions. AIM: To evaluate the long-term feasibility of a novel heterogenous ada-BD for treating extrahepatic BDI in pigs. METHODS: Eight pigs were randomly divided into two groups in the study. The animal injury model was developed with an approximately 2 cm segmental defect of various parts of the common bile duct (CBD) for all pigs. A 2 cm long novel heterogenous animal-derived bile duct was used to repair this segmental defect (group A, ada-BD-to-duodenum anastomosis to repair the distal CBD defect; group B, ada-BD-to-CBD anastomosis to repair the intermedial CBD defect). The endpoint for observation was 6 mo (group A) and 12 mo (group B) after the operation. Liver function was regularly tested. Animals were euthanized at the above endpoints. Histological analysis was carried out to assess the efficacy of the repair. RESULTS: The median operative time was 2.45 h (2-3 h), with a median anastomosis time of 60.5 min (55-73 min). All experimental animals survived until the endpoints for observation. The liver function was almost regular. Histologic analysis indicated a marked biliary epithelial layer covering the neo-bile duct and regeneration of the submucosal connective tissue and smooth muscle without significant signs of immune rejection. In comparison, the submucosal connective tissue was more regular and thicker in group B than in group A, and there was superior integrity of the regeneration of the biliary epithelial layer. Despite the advantages of the regeneration of the bile duct smooth muscle observed in group A, the effect on the patency of the ada-BD grafts in group B was not confirmed by macroscopic assessment and cholangiography. CONCLUSION: This approach appears to be feasible for repairing a CBD defect with an ada-BD. A large sample study is needed to confirm the durability and safety of these preliminary results.

[Effect of histamine H4 receptor and its antagonist on allergic rhinitis in rats].

OBJECTIVE: To clarify the effect of histamine H4 receptor antagonist, JNJ 7777120, and histamine H1 receptor antagonist, Loratadine, on allergic rhinitis (AR) in rats and to study the role of histamine H4 receptor antagonist and histamine H1 receptor antagonist in the pathogenesis of allergic rhinitis and therapeutic value of their antagonist. METHODS: AR animal model were induced by ovalbumin (OVA) in the Wistar rats, which treated with histamine H4 receptor antagonist and (or) histamine H1 receptor antagonist. The allergic symptoms (sneezing and nasal rubbing), serum total IgE and the levels of cytokines in serum or nasal lavage fluid were measured, the diversity between two groups were observed. Statistical analysis was performed using a SPSS 13.0 software. RESULTS: Compared with AR group with no treatment, the inhibition of nasal symptoms (P < 0.01), a significant decrease in the levels of IgE, IL-4 in serum and Eotaxin in nasal lavage fluid (P < 0.01), a significant increase in the levels of IFN-γ in serum (P < 0.01) after treatment was found. Compared with group treated with Loratadine, inhibition of nasal symptoms (q value were 3.72, 4.16, P < 0.01), a significant increase in the levels of IgE and IL-4 in serum (q value were 8.01, 4.96, P < 0.05), a significant decrease in the levels of IFN-γ in serum (q = 3.18, P < 0.05) in group treated with JNJ 7777120 also, but no significant differences in the levels of Eotaxin in nasal lavage fluid (P > 0.05). Administration of JNJ 7777120 and Loratadine jointly, neither additive effect nor synergistic action were found (P > 0.05). CONCLUSIONS: Histamine H4 receptor is closely related with allergic rhinitis and is important in the pathogenesis of allergic rhinitis, the same as histamine H1 receptor. Histamine H4 receptor antagonist, JNJ 7777120, could relieve symptoms and inflammatory conditions in allergic rhinitis, the effect was weak compared with Loratadine. Neither additive effect nor synergistic action were found between them.

[Mechanism of endogenous carbon monoxide effect on hydrogen sulfide in guinea pigs with established allergic rhinitis].

OBJECTIVE: To study the effect of carbon monoxide (CO) on hydrogen sulfide (H2S) in guinea pigs with allergic rhinitis (AR) through intervention treatment. METHODS: AR model in guinea pigs was established by using ovalbumin. The animals were divided into three groups. Group one was sensitized continuously by ovalbumin, group two was treated with Hemin as induction group, and group three was treated with zinc protoporphyrin (ZnPP) as suppression group. The guinea pigs treated with saline were used as control. The behavior science scores, eotaxin concentration of nasal lavage, IgE in blood serum were recorded, and the plasma concentrations of CO and H2S were determined, then the expression of hemeoxygenase (HO)-1, cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) were measured in nasal mucosa by fluorescent quantitative RT-PCR. RESULTS: The behavior science scores, concentration of eotaxin in nasal lavage, IgE in blood serum and concentration of CO in plasma of sensitized group were higher than those of control (P<0.01), and the expression of HO-1 in nasal mucosa was also higher than control [(7.61+/-2.80)x10(-3) vs (2.32+/-1.14)x10(-3), P<0.05]. All these items were higher when treated with Hemin and lower when treated with ZnPP (P<0.05). The concentration of H2S in plasma was lower than control with significant differences [(14.80+/-1.60) micromol/L vs (18.90+/-1.00) micromol/L, P<0.01], the expression of CSE was also lower than control (P<0.05), and both of them were lower with Hemin induced and higher with ZnPP (P<0.05). The expression of CBS was very low and had no significant differences between groups (P>0.05), so it indicated that the CSE was the key enzyme for endogenous H2S product in nasal mucosa. Moreover the concentration of H2S was negatively correlated with CO (r=-0.702, P<0.001). CONCLUSIONS: Endogenous CO and H2S play a significant role in the pathogenesis of AR, and HO-1 and CSE are the main speed-relate enzymes respectively. The H2S is also influenced by CO.

[Influence of carbon monoxide on the expression of inducible nitric oxide synthase mRNA in guinea pigs with allergic rhinitis.].

OBJECTIVE: To study the impact of carbon monoxide (CO) on expression levels of inducible nitric oxide synthase (iNOS) mRNA in guinea pigs with allergic rhinitis (AR). METHODS: Twenty four guinea pigs were divided randomly into four study groups with 6 guinea pigs in each. The guinea pigs in the first group were treated with saline only (Group 1, the healthy controls). The remaing guinea pigs were sensitized by ovalbumin and thus establishing the AR models. After sensitization, the animals in the second group remained untreated (Group 2, AR control group). The third group was treated with Hemin as the induction group, and the fourth group was treated with Zinc protoporphyrin (ZnPP) as the suppression group. The plasma concentration of carboxyhemoglobin (COHb) was measured, which represents the concentration of CO. The expression levels of Heme oxygenase-1 (HO-1) and NOS mRNAs in nasal mucosa were determined by fluorescent quantitative RT-PCR. RESULTS: AR models were established successfully in all study guinea pigs. The concentrations of COHb (x(-) +/- s) in plasma of the second group (2.27% +/- 1.13%) were significantly (q = 4.10, P < 0.01) higher than those of healthy controls (1.08% +/- 0.24%). The plasma concentration of COHb in the third group (3.17% +/- 0.68%) were also significantly higher (q = 3.12, P < 0.05) than those in the second group. The expression levels of HO-1 and iNOS in nasal mucosa of the second group [(7.80 +/- 1.60) x 10(-3) and (5.81 +/- 0.05) x 10(-3), respectively] were also significantly (q equals 5.52 and 7.21, respectively, P < 0.01) higher than those of controls [(1.96 +/- 0.71) x 10(-3) and (0.97 +/- 0.05) x 10(-3), respectively]. The expression levels of HO-1 and iNOS in the nasal mucosa of the third group [(11.89 +/- 4.78) x 10(-3) and (7.42 +/- 0.70) x 10(-3), respectively] were significantly (q equals 3.86 and 2.22, P < 0.05) higher than those of the second group. The expression levels of HO-1 and iNOS in nasal mucosa of the fourth group [(3.82 +/- 0.98) x 10(-3) and (2.34 +/- 0.04) x 10(-3), respectively] were significantly (q equals 3.76 and 5.18, P < 0.05) lower than those in the second group. CONCLUSIONS: Endogenous carbon monoxide influenced the expression levels of iNOS in nasal mocusa in guinea pigs with AR.

[Detection of microcystin-LR in waters using indirect competitive ELISA].

Indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was established to detect microcystin-LR in waters, with the concentration of the complete antigen was 5microg/mL, the dilution of the monoclonal antibody was 1:3,000, the dilution of the enzyme tracer (goat anti-rabbit IgG-peroxidase) was 1:3,000, the concentration range of microcystin-LR was between 0.001 approximately 30microg/L, and using o-phenylenediamine as substrate. The assay showed a high relativity of more than 99% with high performance liquid chromatography, a mean relative standard deviation less than 10% , a detection limitation under 0.01microg/L and quantitative detection range was 0.01 approximately 3microg/L, high specificity for [4-arginine] microcystin, and it could still perform well under the influence from the samples.