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.

Diphosphine Ligand-Enabled Nickel-Catalyzed Chelate-Assisted Inner-Selective Migratory Hydroarylation of Alkenes.

The precise control of the regioselectivity in the transition metal-catalyzed migratory hydrofunctionalization of alkenes remains a big challenge. With a transient ketimine directing group, the nickel-catalyzed migratory ß-selective hydroarylation and hydroalkenylation of alkenyl ketones has been realized with aryl boronic acids using alkyl halide as the mild hydride source for the first time. The key to this success is the use of a diphosphine ligand, which is capable of the generation of a Ni(II)-H species in the presence of alkyl bromide, and enabling the efficient migratory insertion of alkene into Ni(II)-H species and the sequent rapid chain walking process. The present approach diminishes organosilanes reductant, tolerates a wide array of complex functionalities with excellent regioselective control. Moreover, this catalytic system could also be applied to the migratory hydroarylation of alkenyl azahetereoarenes, thus providing a general approach for the preparation of 1,2-aryl heteroaryl motifs with wide potential applications in pharmaceutical discovery.

Case Report: A Rare Case of Nasal Forehead Mass in Kimura's Disease.

Background: Kimura's disease is a rheumatic immune disease and head and neck lymph nodes are often involved. A mass occurring in the nasal forehead is rare. Good prognosis after surgical resection by glucocorticoid therapy is more rare. Case Summary: We report the rare case of a nasal forehead mass in a 45-year-old male patient with Kimura's disease. The patient underwent resection of the mass in October 2018 in a local hospital and the postoperative pathology was unclear. He then underwent a second resection in our department in December 2019 mainly because growth of the mass was affecting his appearance. Postoperative pathology confirmed that the patient had Kimura's disease, and he accepted systemic treatment with prednisone. We followed the patient for 10 months after surgery. He is now recovering well and continues to be closely monitored during follow-up. Conclusion: It is rare that the painless mass in the nasal forehead is diagnosed as a Kimura's disease.After completely resection of the mass and systemic treatment with prednisone, the patient had a good outcome. We provide experience for the treatment of Kimura's disease in nasal forehead.

Osthole induces cell cycle arrest and apoptosis in head and neck squamous cell carcinoma by suppressing the PI3K/AKT signaling pathway.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common lethal tumors with a high recurrence rate and low survival rate. Therefore, an urgent need exists for novel and effective treatment strategies for HNSCC patients. METHODS: Osthole, a natural ingredient extracted from Cnidium monnieri (L.) 'Cusson', has multiple pharmacological effects including antineoplastic activity. Regrettably, the antineoplastic effect of osthole in HNSCC cells remains undefined. We utilize in vitro assays to assess the anti-proliferative effects of osthole in HNSCC cells and tumorigenesis assays using FaDu cells in murine HNSCC models to assess in vivo function. Moreover, the possible molecular mechanisms of Osthole on HNSCC cells was also investigated. RESULTS: Our findings show that the anti-proliferation effect of osthole might function through induction of cell cycle arrest (G2/M phase) and apoptosis in HNSCC. Osthole could also down-regulating the protein level of cell cycle and apoptosis related proteins, such as Bcl-2, PARP1, Survivin, CyclinB1 and Cdc2, while up-regulating expression of Cleaved Caspase3/9, Cleaved PARP1 and Bax. Similarly, osthole suppressed the in vivo growth of FaDu cells in a subcutaneous tumor model. In terms of mechanism, our data show that osthole can suppress the PI3K/AKT pathway. CONCLUSIONS: In the current study, our in vitro and in vivo assay showed the suppressive effect of Osthole on HNSCC cells through induce cell cycle arrest (G2/M phase) and apoptosis. Moreover, the action mechanisms of Osthole on proliferation related signaling pathways was disclosed. Our present study suggests that osthole might be used as an effective therapeutic agent for patients with HNSCC.

Computer-aided identification of protein targets of four polyphenols in Alzheimer's disease (AD) and validation in a mouse AD model.

Natural polyphenols are a large class of phytochemicals with neuroprotective effects. Four polyphenolic compounds: hesperidin, icariin, dihydromyricetin and baicalin were selected to evaluate their effects on Alzheimer's disease (AD). We analyzed by an inverse docking procedure (INVDOCK) the potential protein targets of these polyphenols within the KEGG AD pathway. Consequently, their therapeutic effects were evaluated and compared in a transgenic APP/PS1 mouse model of AD. These polyphenols were docked to several targets, including APP, BACE, PSEN, IDE, CASP, calpain and TNF-α, suggesting potential in vivo activities. Five month old transgenic mice were treated with these polyphenols. Icariin and hesperidin restored behavioral deficits and ameliorated Aß deposits in both the cortex and hippocampus while baicalin and dihydromyricetin showed no substantial effects. Our findings suggest that hesperidin and icariin could be considered potential therapeutic candidates of human AD.

T-Helper Type 9 Cells Play a Central Role in the Pathogenesis of Respiratory Epithelial Adenomatoid Hamartoma.

The etiology and pathogenesis of respiratory epithelial adenomatoid hamartoma (REAH) remain poorly understood, although some reports have suggested that REAH features an inflammatory process. T-helper type 9 (Th9) cells are a newly identified subset of CD4 T-helper cells characterized by the expression of high levels of interleukin (IL)-9, which may promote inflammation. As REAH may involve an inflammatory process, we evaluated whether IL-9 and/or Th9 cells were present in REAH and compared the levels thereof to those of normal nasal mucosa. Eleven patients with REAH and 5 exhibiting cerebrospinal fluid leakage were included in the study. Flow cytometry was used to measure Th9 cell numbers, a cytometric bead assay was applied to measure IL-9 levels, and real-time polymerase chain reaction was used to quantify the levels of mRNA encoding IL-9. Th9 cells, IL-9 mRNA, and IL-9 were detected in all REAH and control samples. The proportion of Th9 cells in the patients with REAH was significantly greater than that in the controls. The expression levels of IL-9-encoding mRNA and IL-9 protein were significantly higher in the patients with REAH than in the controls. The Th9 cell subset was expanded, the synthesis of IL-9-encoding mRNA was upregulated, and IL-9 secretion was increased in REAH tissue, suggesting that Th9 cells play a central role in the pathogenesis of the disease.

Proteomic characterization of the possible molecular targets of pyrrolizidine alkaloid isoline-induced hepatotoxicity.

Pyrrolizidine alkaloids (PAs) are distributed in plants worldwide including medicinal herbs or teas. In the present study, we investigated the effects of isoline, which is a retronecine-type PA isolated from traditional Chinese medicinal herb Ligularia duciformis, on mouse liver proteins by using proteomic approaches. Firstly, our results showed that 110mg/kg isoline increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum, and hepatic tissue pathological observation further confirmed isoline-induced liver injury. Proteomic analysis showed that the liver samples from mice of isoline group demonstrated about 13 differentially expressed proteins compared with normal group, and those proteins may be involved in isoline-induced liver injury in mice. Next, all these 13 protein spots were identified by MALDI-TOF-TOF MS or LTQ MS; and among them 9 differentially expressed proteins are involved in the process of oxidative stress or cellular energy metabolism. Further lipid peroxidation analysis and ATPase assay confirmed the existing of oxidative injury induced by isoline and consequent disruption of energy metabolism. Furthermore, an in silico drug target searching program INVDOCK identified 2 potential protein targets of isoline, and the results are in support of proteomic analysis. In summary, the possible signaling molecules related with isoline-induced liver injury were demonstrated in this study.

Clarifying the signal network of salvianolic acid B using proteomic assay and bioinformatic analysis.

Salvianolic acid B (SB) is a natural compound with protective effect against ischemia-reperfusion heart injury. However, the signal network of SB including both direct target proteins and downstream signal-related proteins has not been clarified. In the present study, epidermal growth factor receptor (EGFR) was predicted to be the most possible direct protein target of SB by INVDOCK, a ligand-protein inverse-docking algorithm. Possible signal-related proteins of SB in H9C2 cells, including both under normal condition and under ischemia-reperfusion injury, were searched using 2-DE analysis. Totally, 14 signal-related proteins were found. Finally, signal network from EGFR to the signal-related proteins was established using bioinformatic analysis. Interestingly, 9 of the 14 signal-related proteins could be included in a network together with EGFR through direct interaction or only one intermediate partner. The signal cascade from EGFR to heat shock protein 27 (HSP27) and mitofilin (IMMT, inner membrane mitochondrial protein) might be the most important cascade. The signal network was certified by measuring the binding affinity of SB to EGFR in vitro, the effect of SB on internalization and phosphorylation of EGFR, the effect of SB on viability and proliferation of H9C2 cells, and the expression of inner membrane mitochondrial protein in the presence of EGFR inhibitor AG 1478.

Cancer classification from the gene expression profiles by Discriminant Kernel-PLS.

Cancer diagnosis depending on microarray technology has drawn more and more attention in the past few years. Accurate and fast diagnosis results make gene expression profiling produced from microarray widely used by a large range of researchers. Much research work highlights the importance of gene selection and gains good results. However, the minimum sets of genes derived from different methods are seldom overlapping and often inconsistent even for the same set of data, partially because of the complexity of cancer disease. In this paper, cancer classification was attempted in an alternative way of the whole gene expression profile for all samples instead of partial gene sets. Here, the three common sets of data were tested by NIPALS-KPLS method for acute leukemia, prostate cancer and lung cancer respectively. Compared to other conventional methods, the results showed wide improvement in classification accuracy. This paper indicates that sample profile of gene expression may be explored as a better indicator for cancer classification, which deserves further investigation.

[Primary thyroid non-Hodgkin's lymphoma of Ann Arbor stages IE and IIE: prognostic factors].

OBJECTIVE: To investigate the prognostic factors of primary non-Hodgkin's thyroid lymphoma. METHODS: From January 1981 to January 2008, 47 patients with stage IE and IIE pathologically confirmed as suffering from B cell non-Hodgkin's lymphoma and treated in hospital, were retrospectively analyzed. Pathology: diffuse large cell B-cell lymphoma (DLBCL) 28, mucosa-associated lymphoma (MALT) 19. The cancer specific survival (CSS) were calculated using the Kaplan-Meier method and compared by the Log-rank test. Age, sex, symptoms, extrathyroid extension, radiation doses, treatment modality and histological type characteristics were evaluated using the Cox regression analysis. RESULTS: The 5-year CSS rate was 61.8%. The 5-year CSS rate for the patients with primary tumor confined to thyroid and with extrathyroid extension were 86.7% and 50.0% (P=0.012). The 5-year CSS rate for the patients treated with radiation doses below 40 Gy and treated to 40 Gy or more were 30.8% and 79.0% (P=0.002). The 5-year CSS rate for the 18 patients with stage II received single modality therapy and the multimodality therapy were 33.3% and 61.1% (P=0.037). The 5-year CSS rate for patients with DLBCL lymphoma lesions and with MALT were 50.0% and 78.9% (P=0.038). Multivariate analysis by Cox regression showed that extrathyroid extension, radiation doses and histological type were independent prognostic factors. CONCLUSIONS: In primary non-Hodgkin's lymphoma of the thyroid, extrathyroid extension, radiation radiation doses and histological type are important prognostic factors. For patients with the stage II received multimodality therapy have a higher CSS than the ones received single-modality therapy.

Simulation of crosstalk between small GTPase RhoA and EGFR-ERK signaling pathway via MEKK1.

MOTIVATION: Small GTPase RhoA regulates cell-cycle progression via several mechanisms. Apart from its actions via ROCK, RhoA has recently been found to activate a scaffold protein MEKK1 known to promote ERK activation. We examined whether RhoA can substantially affect ERK activity via this MEKK1-mediated crosstalk between RhoA and EGFR-ERK pathway. By extending the published EGFR-ERK simulation models represented by ordinary differential equations, we developed a simulation model that includes this crosstalk, which was validated with a number of experimental findings and published simulation results. RESULTS: Our simulation suggested that, via this crosstalk, RhoA elevation substantially prolonged duration of ERK activation at both normal and reduced Ras levels. Our model suggests ERK may be activated in the absence of Ras. When Ras is overexpressed, RhoA elevation significantly prolongs duration of ERK activation but reduces the amount of active ERK partly due to competitive binding between ERK and RhoA to MEKK1. Our results indicated possible roles of RhoA in affecting ERK activities via MEKK1-mediated crosstalk, which seems to be supported by indications from several experimental studies that may also implicate the collective regulation of cell fate and progression of cancer and other diseases.

Proteomics characterization of the cytotoxicity mechanism of ganoderic acid D and computer-automated estimation of the possible drug target network.

Triterpenes isolated from Ganoderma lucidum could inhibit the growth of numerous cancer cell lines and were thought to be the basis of the anticancer effects of G. lucidum. Ganoderic acid D (GAD) is one of the major components in Ganoderma triterpenes. GAD treatment for 48 h inhibited the proliferation of HeLa human cervical carcinoma cells with an IC(50) value of 17.3 +/- 0.3 microM. Flow cytometric analysis and DNA fragmentation analysis indicated that GAD induced G(2)/M cell cycle arrest and apoptosis. To identify the cellular targets of GAD, two-dimensional gel electrophoresis was performed, and proteins altered in expressional level after GAD exposure of cells were identified by MALDI-TOF MS/MS. The regulation of proteins was also confirmed by Western blotting. The cytotoxic effect of GAD was associated with regulated expression of 21 proteins. Furthermore these possible GAD target-related proteins were evaluated by an in silico drug target searching program, INVDOCK. The INVDOCK analysis results suggested that GAD could bind six isoforms of 14-3-3 protein family, annexin A5, and aminopeptidase B. The direct binding affinity of GAD toward 14-3-3 zeta was confirmed in vitro using surface plasmon resonance biosensor analysis. In addition, the intensive study of functional association among these 21 proteins revealed that 14 of them were closely related in the protein-protein interaction network. They had been found to either interact with each other directly or associate with each other via only one intermediate protein from previous protein-protein interaction experimental results. When the network was expanded to a further interaction outward, all 21 proteins could be included into one network. In this way, the possible network associated with GAD target-related proteins was constructed, and the possible contribution of these proteins to the cytotoxicity of GAD is discussed in this report.

Computer prediction of drug resistance mutations in proteins.

Drug resistance is of increasing concern in the treatment of infectious diseases and cancer. Mutation in drug-interacting disease proteins is one of the primary causes for resistance particularly against anti-infectious drugs. Prediction of resistance mutations in these proteins is valuable both for the molecular dissection of drug resistance mechanisms and for predicting features that guide the design of new agents to counter resistant strains. Several protein structure- and sequence-based computer methods have been explored for mechanistic study and prediction of resistance mutations. These methods and their usefulness are reviewed here.

[Clinical observation and histological research of vocal cord's reformation after laser cordectomy].

OBJECTIVE: Explore the reformation of new vocal cord after laser cordectomy and the histological change of new vocal cord by animal experiment. METHODS: The reforming course of new vocal cord was observed by follow-up. 4 dogs underwent bilateral cordectomy (type II operation) and their larynx were analyzed anatomically and histologically eight months later. 100 cases who underwent KTP laser cordectomy were divided into 3 types according to the range and depth of the excision. RESULTS: All the dogs had reformation of vocal cords eight months later. On the surface of the reformed vocal cord, no mucous cell but squamous cells was found. Newborn ligament-like connective tissues and loose muscle fibers were found under membrane. Complete reconstruction of larynx was found in 16 cases of type I (16/16) and 54 of type II 86% (54/63). But in type III no new vocal cord was found. CONCLUSION: Formation of the new vocal cord is the result of hypertrophy of the remained vocal cord muscle, influenced by depth of the excised vocal cord using laser. The histological construction is nearly normal cord. Whether or not the laser radiation stimulate the tissue hypertrophy is need more research.