Olfactory disorders are a common symptom in patients with chronic rhinosinusitis, and their diagnosis and treatment have garnered extensive attention from both patients and doctors. Currently, there are various evaluation and treatment methods for olfactory dysfunction; however, choosing a simpler and more accurate assessment, as well as an effective treatment, remains a clinical challenge. In this article, we review the assessment and treatment methods commonly used in clinical practice in recent years to provide better support for the diagnosis and treatment of olfactory disorders.
Humans ; Olfaction Disorders/etiology* ; Sinusitis/complications* ; Chronic Disease ; Rhinitis/complications* ; Rhinosinusitis

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.

Objective To investigate the relationship between primary pulmonary mucinous adenocarcinoma (PPMA) mass type and pneumonia type and their difference in malignant degree, and to analyze the role of clinical manifestations and CT features in the diagnosis of this disease. Methods The clinical data of PPMA patients admitted in the First Affiliated Hospital of Xiamen University from May 2011 to March 2022 were retrospectively analyzed. According to CT features, they were divided into a mass type group and a pneumonia type group. The clinical manifestations, CT features and the degree of malignancy between the two groups were analyzed and compared. Results A total of 57 PPMA patients were enrolled. There were 17 males and 40 females, with an average age of (53.82±10.65) years, and 28 (49%) patients had reversed hato-like sign. There were 42 patients in the mass type group and 15 patients in the pneumonia type group. PPMA often occurs in both lower lungs, with clinical manifestations mainly of coughing and expectorating white mucoid sputum. There were statistical differences between the two groups in the maximum diameter of tumor (P<0.001), boundary condition (P<0.001) and pleural indentation sign (P=0.019). There was no statistical difference between the two groups in Ki-67 index (P>0.05). Conclusion There is no statistical difference in the degree of malignancy between the two types of PPMA. Considering their clinical manifestations and differences in imaging features, it is supported that the pneumonia type is just a progression of the mass type. CT can present various manifestations, among which the reversed hato-like sign is expected to become an important imaging feature. Combined with a high proportion of solid components, pleural indentation sign, and vacuole sign, reversed hato-like sign can play a significant role in the diagnosis of PPMA.

Objective:To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province.Methods:A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Approval Number: 2019 Medical Ethics Review No. 67). Results:Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c. 1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c. 467G>A (p.Gly156Asp) and c. 1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c. 1297G>C (p.Ala433Pro) and c. 1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and may affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. Conclusion:The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c. 1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.

Objective:To determine the prevalence of GJB2 gene c. 109G>A (p.V37I) variant among infants with congenital hearing loss and analyze the initial audiological characteristics of children harboring the variant, compare the audiometric difference among individuals with various genotypes, and explore genetic and audiological manifestations of the affected families. Methods:One hundred twenty six infants diagnosed with congenital hearing loss at the Neonate Screening Center of Ningbo City from June 2021 to December 2024 were selected as the study subjects. The neonates, in addition with members from 16 of their families, had undergone genetic screening for variants of 208 hotspot sites within 24 deafness-associated genes. For cases identified with monoallelic variants and concurrent hearing loss, the full GJB2 gene was sequenced. Meanwhile, a retrospective analysis was carried out on 23 children whom were confirmed to have hearing loss and the c. 109G>A variant by whole exome sequencing from March 2022 to December 2024. And 102 children who were excluded to have hearing loss and pathogenic variants by whole exome sequencing were selected as normal controls. Audiological features of individuals harboring the c. 109G>A variant were compared. This study has been approved by the Medical Ethics Committee of The Affiliated Women and Children′s Hospital of Ningbo University (Ethics No.: EC2023-009). Results:For the 126 infants with congenital hearing loss, prospective screening has identified 58 (46.03%) to harbor the c. 109G>A variant. These included 38 homozygotes and 16 compound heterozygotes. Retrospective review of the 23 c. 109G>A positive children has identified 15 as homozygotes and 8 as compound heterozygotes. Genetic testing of the 16 pedigrees has identified 7 homozygotes and 1 compound heterozygote. For the homozygotes combined ( n=53), 96.2% exhibited bilateral symmetric hearing loss, with 78.3% showing high-frequency sloping patterns, and 98.1% having a hearing threshold ranging from 20 to 65 dB. For the compound heterozygotes combined ( n=24), 95.8% showed symmetric loss, with 59.4% having high-frequency sloping, and 97.9% had a hearing threshold ranging from 20 to 65 dB. Both groups showed significantly elevated ABR/PTA thresholds compared with the normal controls ( P=0.000). The compound heterozygous group had higher ABR thresholds (43.3 ± 15.0 dB nHL) compared with the homozygous group (39.1±12.0 dB nHL, P=0.005). Conclusion:Infants harboring the GJB2 c. 109G>A variant primarily manifest as mild-to-moderate, symmetric, high-frequency sloping hearing loss. Nearly one-third of affected children have thresholds between 20 to 35 dB nHL, suggesting that ABR > 35 dB nHL alone may underestimate the hearing impairment in this population. Compared with homozygotes, compound heterozygotes with the the GJB2 c. 109G>A variant can confer a more severe hearing loss.

Objective:To discuss the effect of KIAA1522 on the proliferation,migration,and invasion of lung cancer cells,and to clarify its signaling mechanism.Methods:Bioinformatics analysis was used to detect the expression levels of KIAA1522 mRNA and protein in 75 cases of human non-small cell lung cancer(NSCLC)tissues and adjacent normal lung tissues;immunohistochemical staining was used to detect the expression of KIAA1522 protein in NSCLC tissue and adjacent normal lung tissues;Western blotting method was used to detect the expression level of KIAA1522 protein in various lung cancer cell lines.KIAA1522-small interfering(siRNA)and over-expression plasmids were transfected into the lung cancer H1299 and A549 cells,respectively.The KIAA1522-siRNA experiment was divided into blank group,negative control group(si-NC group),KIAA1522-siRNA#1 group,and KIAA1522-siRNA#2 group.The KIAA1522 over-expression experiment was divided into control group,empty vector control group(OE-NC group,transfected with KIAA1522 over-expression empty vector plasmid),KIAA1522 overexpression group(OE-KIAA1522 group,transfected with KIAA1522 over-expression plasmid),KIAA1522 over-expression+MK2206 group[OE-KIAA1522+MK2206 group,co-transfected with KIAA1522 over-expression plasmid and protein kinase B(AKT)signaling pathway inhibitor MK2206],and MK2206 group(transfected with MK2206).Western blotting method was used to verify the transfection efficiencies of the cells in various groups;MTT assay was used to detect the proliferation activities of the lung cancer cells in various groups;cell scratch assay was used to detect the migration rates of lung cancer cells in various groups;Transwell chamber assay was used to detect the numbers of invasion lung cancer cells in various groups;Western blotting method was used to detect the expression levels of phosphorylated AKT(p-AKT),total AKT(t-AKT),cyclin D1(Cyclin D1),vascular endothelial growth factor(VEGF),and epithelial-mesenchymal transition(EMT)-related proteins[vimentin(Vimentin),N-cadherin(N-cadherin),and E-cadherin(E-cadherin)]proteins in the cells in various groups.Results:The bioinformatics analysis results showed that compared with adjacent normal lung tissue,the expression levels of KIAA1522 mRNA and protein in NSCLC tissue were significantly increased(P<0.05 or P<0.01).The immunohistochemistry staining results showed that compared with adjacent normal lung tissue,the positive expression rate of KIAA1522 protein in NSCLC tissue was significantly increased(P<0.05)and was associated with TNM stage(P<0.01).The Western blotting results showed that compared with normal lung epithelial cells BEAS-2B,the expression levels of KIAA1522 protein in lung cancer cell lines PC9,H1299,H460,A549,H1975,and H226 were significantly increased(P<0.05 or P<0.01).Compared with si-NC group,the expression levels of KIAA1522 protein in the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the expression level of KIAA1522 protein in the A549 cells in OE-KIAA1522 group was significantly increased(P<0.01).The MTT results showed that at 24,48,and 72 h of cell culture,compared with si-NC group,the proliferation activities of the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the proliferation activity of the A549 cells in OE-KIAA1522 group was significantly increased(P<0.05);compared with OE-KIAA1522 group,the proliferation activity of the A549 cells in OE-KIAA1522+MK2206 group was significantly decreased(P<0.01);compared with OE-KIAA1522+MK2206 group,the proliferation activity of the A549 cells in MK2206 group was significantly decreased(P<0.05).The cell scratch assay results showed that compared with si-NC group,the migration rates of the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the migration rate of the A549 cells in OE-KIAA1522 group was significantly increased(P<0.01);compared with OE-KIAA1522 group,the migration rate of the A549 cells in OE-KIAA1522+MK2206 group was significantly decreased(P<0.05);compared with OE-KIAA1522+MK2206 group,the migration rate of the A549 cells in MK2206 group was significantly decreased(P<0.05).The Transwell chamber assay results showed that compared with si-NC group,the numbers of invasion H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the number of invasion A549 cells in OE-KIAA1522 group was significantly increased(P<0.01);compared with OE-KIAA1522 group,the number of invasion A549 cells in OE-KIAA1522+MK2206 group was significantly decreased(P<0.01);compared with OE-KIAA1522+MK2206 group,the number of invasion A549 cells in MK2206 group was significantly decreased(P<0.01).The Western blotting results showed that compared with si-NC group,the expression levels of p-AKT,Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly increased(P<0.01);compared with OE-NC group,the expression levels of p-AKT,Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the A549 cells in OE-KIAA1522 group were significantly increased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly decreased(P<0.05);compared with OE-KIAA1522 group,the expression levels of p-AKT,Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the A549 cells in OE-KIAA1522+MK2206 group were significantly decreased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly increased(P<0.05);compared with OE-KIAA1522+MK2206 group,the expression levels of Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the A549 cells in MK2206 group were significantly decreased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly increased(P<0.05).Conclusion:The KIAA1522 protein upregulates the expression of Cyclin D1,EMT-related proteins,and VEGF protein in lung cancer cells,promoting the proliferation,migration,and invasion of lung cancer cells,and its mechanism is related to the activation of the AKT signaling pathway.

OBJECTIVE To analyze the peak wideband acoustic immittance(WAI)values reflecting the tympanic membrane absorption characteristics during the measurement process in patients with congenital middle ear malformation.METHODS We selected 36 patients diagnosed with congenital middle ear malformation by CT as subjects and evaluated their tympanic membrane absorption characteristics by measuring their acoustic impedance peak pressure.Then,we divided these data into two groups based on the pathological malformation obseved during the surgical process,namely the auditory ossicular chain soft connection group and the auditory ossicular chain fixation group.Calculate the absorption rate values of the tympanic membrane at each frequency corresponding to the peak pressure value of the tympanogram,and the relative area of absorption rate.By conducting independent t-tests,we compared two groups-normal children and patients who had undergone ossicular chain fixation surgery-to analyze the absorption area and peak absorption rate of their tympanic peak pressure values.RESULTS Under peak pressure,there were significant differences(P<0.001)in the full frequency range tympanic membrane absorption rate and peak absorption rate between the group with fixed ossicular chain and the normal group.However,there was no difference in the full frequency range tympanic membrane absorption rate and peak absorption rate between the group with soft ossicular chain and the normal group.Under peak pressure,the absorption area of the ossicular chain fixation group was significantly lower than that of the normal group in the low frequency range of 226-1 000 Hz(P<0.001),while the absorption area of the ossicular chain soft connection group was significantly higher than that of the normal group in the low frequency range of 226-1 000 Hz(P<0.001).CONCLUSION When conducting broadband acoustic impedance test,there is a significant difference in the relative area of tympanic membrane absorption rate of acoustic impedance peak pressure between the auditory ossicular chain soft connection group and the auditory ossicular chain fixation group across 226-1 000 Hz.It has application value as a clinical rapid screening and diagnostic tool for middle ear malformations.

Objective:To explore the clinical efficacy of percutaneous balloon compression (PBC) in the treatment of trigeminal neuralgia (TN) based on the double difference (DID) model.Methods:A retrospective case - control study method was adopted to analyze the general data of 130 patients with trigeminal neuralgia (TN) who were treated in the Department of Neurosurgery of Hebei General Hospital from January 2022 to October 2023. Among them, 49 were males and 81 were females. The age was (53.28±11.67) years, ranging from 25 to 80 years old. According to different treatment methods, the patients were divided into an experimental group ( n=63) and a control group ( n=67). Patients in the experimental group were given percutaneous balloon compression (PBC) treatment, while those in the control group were treated with conservative drug therapy. Propensity score matching method was used for 1∶1 matching. After matching, there were 52 cases in each group. The general data of the two groups were compared. The visual analogue scale (VAS), 36-item short form health survey (SF-36) score, Hamilton depression rating scale (HAMD) score, Hamilton anxiety rating scale (HAMA) score, 5-hydroxytryptamine, neuropeptide P, inflammatory factor interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) before and after treatment, as well as the clinical efficacy of the two groups of patients were comparatively analyzed. Meanwhile, the incidence of postoperative complications in the two groups was compared. The generalized estimating equation (GEE) model was used to analyze the influencing factors of clinical efficacy, and the difference-in-differences (DID) model was used to evaluate the efficacy before and after treatment. Measurement data conforming to the normal distribution were expressed as mean±standard deviation ( ± s), and the t-test was used for comparison between groups; the chi- square test was used for comparison between count data. Results:After treatment, the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, and TNF-α level in the experimental group were (2.98±0.83) points, (75.56±1.18) points, (7.2±0.83) points, (7.15±0.85) points, (76.34±5.47) ng/mL, (50.95±11.01) pg/mL, (29.45±7.08) ng/L, and (21.18±3.55) ng/L respectively. In the control group, there were (3.63±0.95) points, (73.23±1.13) points, (7.98±0.80) points, (8.04±0.84) points, (186.31±11.61) ng/mL, (86.52±13.32) pg/mL, (34.47±6.58) ng/L, and (26.36±5.80) ng/L, respectively. The differences between the two groups were statistically significant ( P<0.05).The cure rate and the total incidence of postoperative complications in the experimental group were 55.77% and 13.46% respectively, while in the control group, they were 40.38% and 30.77% respectively. The differences between the two groups were statistically significant ( P<0.05).The results of the GEE model analysis showed that age, course of disease, VAS, SF-36 score, HAMA score, HAMD score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, TNF-α level, treatment method, and the long - diameter ratio of FO significantly affected the clinical efficacy of patients ( P<0.05).The results of the DID model showed that the experimental group was superior to the control group in improving the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, and TNF-α level( P<0.05). Conclusion:PBC can significantly improve the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine, neuropeptide P, IL-1, TNF-α, and incidence of complications in patients with TN. It can also improve the psychological status and quality of life of patients.