SIRT5 exacerbates eosinophilic chronic rhinosinusitis by promoting polarization of M2 macrophage.

BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.

[Application of metal cushion block combined with Jumbo cup in reconstruction of acetabular bone defect in revision of artificial hip joint].

OBJECTIVE: To investigate the application effect and imaging changes of metal cushion block combined with Jumbo cup in the reconstruction of acetabular bone defect after revision of artificial hip joint. METHODS: Retrospective analysis was made on the clinical data of 83 patients who underwent revision acetabular bone defect reconstruction of the artificial hip joint in our hospital from September 2019 to October 2021. They were divided into group A and group B according to different surgical methods. There were 42 patients in group A, including 26 males and 16 females, aged from 44 to 72 years old with an average of (60.57±4.62) years, who underwent revision with metal cushion block and Jumbo cup. There were 41 patients in group B, including 22 males and 19 females, aged from 42 to 71 years old with an average of (58.74±4.25) years, who underwent revision with metal cushion block and bone cement mortar cup. The operation related indexes, Harris hip function score and visual analogue scale (VAS) of pain before operation, 1 month and 12 month after operation were compared between two groups. The results of X-ray imaging examination (hip rotation center height, acetabular abduction angle, femoral eccentricity and imaging standard qualification rate) before and 12 month after operation were evaluated, and the incidence of complications was compared between two groups. RESULTS: There was no significant difference in operation time, intraoperative bleeding volume and postoperative drainage volume between two groups (P>0.05). Both groups were followed up for 12 to 36 months with an average of (25.36±3.59) months. The scores of pain, function, deformity and Harris' total score in the two groups at 1 month after operation were higher than those before operation (P<0.05), and the scores of pain, function, deformity, joint activity and Harris' total score in two groups at 1 year after operation were higher than those before operation and 1 month after operation (P<0.05), and the above scores in group A were higher than those in group B at 1 year after operation (P<0.05). The VAS of two groups decreased successively at 1 month and 1 year after operation (P<0.05), but there was no significant difference in both groups at each time point (P>0.05). The femoral eccentricity increased in both groups at 1 year after operation (P<0.05), and group A was higher than group B (P<0.05). The height of rotation center and acetabular abduction angle decreased in both groups at 1 year after operation (P<0.05), and the height of rotation center in group A was lower than that in group B (P<0.05), but there was no significant difference in acetabular abduction angle between two groups (P>0.05). The imaging qualification rate of group A was higher than that of group B (P<0.05). There was no significant difference in the incidence of adverse reactions between two groups (P>0.05). CONCLUSION: Metal cushion block combined with Jumbo cup in the treatment of acetabular bone defects can provide the hip joint function, and restore the hip joint rotation center, femoral eccentricity and acetabular abduction angle, with obvious clinical effect.

Analysis of Diagnosis and Treatment Strategies for Primary Juvenile Psammomatoid Ossifying Fibroma Complicated With Primary Aneurysmal Bone Cyst.

BACKGROUND: Juvenile Psammomatoid Ossifying Fibroma (JPOF) is a type of noncancerous bone tumor that usually affects adolescents in the craniomaxillofacial area. Clinical manifestations are usually symptoms caused by the tumor's invasive compression of surrounding tissues. Aneurysmal Bone Cyst (ABC) is also a benign bone tumor, and it typically occurs in long bones and the spine. Only 2% to 3% of cases occur in the head and neck. Due to the rarity of this combination of clinical cases, clinicians face difficulties in comprehensively understanding this complex lesion. Therefore, a comprehensive review of the clinical manifestations and characteristic imaging findings is necessary for surgeons. CASE PRESENTATIONS: On April 6, 2019, a 13-year-old boy presented with left maxillofacial bulge and pain for 1 month. Magnetic resonance imaging of the paranasal sinuses showed an irregular hive-like mass signal in the left maxillary sinus, and cystic changes with fluid levels were seen in the lesion. After the initial diagnosis of JPOF with primary ABC, we decided to perform a facial mid-facial resection of maxillary sinus tumor to remove the tumor tissue. Finally, after 3 recurrences and 4 operations, there was no tumor recurrence for 20 months after the last operation, and the patient was still under continuous follow-up. CONCLUSIONS: This case provided a reference for the diagnosis and treatment of JPOF combined with ABC. In particular, a new understanding of the association between the two diseases and the management of recurrence were proposed, which had the potential to improve clinical understanding of this complicated condition.

Factors associated with human papillomavirus persistence after loop electrosurgical excision procedure in patients with cervical squamous intraepithelial lesion.

AIM: To seek the high-risk factors of human papillomavirus (HPV) persistence and residual lesion or recurrence after loop electrosurgical excision procedure (LEEP) focus on the predictive value of intraoperative human papilloma virus (IOP-HPV) testing. METHODS: Intraoperative endocervical sample was obtained with a cytobrush from the remained cervix of 292 patients immediately after LEEP. HPV Genotyping was performed using a polymerase chain reaction technique. All patients followed by HPV genotyping and cytology every 3-6 months. The IOP-HPV testing results and possible risk factors such as age, cytology grade, menopause status, margin involvement, preoperative HPV status, and cervical lesion grade were assessed in predicting persistence of HPV and residual lesion or recurrence after surgery. RESULTS: There were 61 (20.9%) patients presented persistent HPV infection. Multivariate analyses showed that IOP-HPV positive, post-menopause and preoperative HPV multiplex infection was strongly associated with HPV persistence after LEEP, IOP-HPV positive and post-menopause was also associated with residua or recurrent disease after LEEP. CONCLUSIONS: IOP-HPV positive, post-menopause, and preoperative HPV multiplex infection are independent predictors of HPV persistence in patients with cervical squamous intraepithelial lesion treated by LEEP. IOP-HPV test is a new approach that may potentially allow for early identification of patients at high risk of HPV persistence and residua or recurrent disease after LEEP, thereby possibly facilitate an attenuated follow-up schedule for negative patients those at low risk of persistent HPV infection.

Blood Eosinophil Percentage and Improved Sinus CT Score as Diagnostic Tools for ECRS.

Objective: Differentiating 2 types of chronic rhinosinusitis with nasal polyps (CRSwNP) is important for the treatment. The current diagnostic methods using single indicators, including peripheral blood eosinophils and traditional sinus computed tomography (CT) scores, are not accurate. In this study, we aimed to investigate the diagnostic value of combining peripheral blood eosinophils and improved sinus CT scores for eosinophic chronic rhinosinusitis (ECRS). Study Design: Retrospective cohort. Setting: Tertiary medical center. Methods: We conducted a study involving 81 patients with CRSwNP. Peripheral blood samples were collected from the non-ECRS and ECRS groups. Improved three-dimensional volume image analysis and Lund-Mackay scoring system were performed to quantify the thickening of sinus mucosa. Multivariate binary logistic regression analysis was carried out to detect the predictive value of the scoring indicators. For significant indexes, receiver operating characteristic (ROC) curve analysis was applied. Results: The ECRS group had higher levels of blood eosinophil percentage and count, ethmoid sinus score, total sinus score, the ratio of ethmoid sinus score and maxillary sinus score, and the difference between ethmoid and maxillary score, compared to the non-ECRS group (P < 0.05). Binary logistic regression analysis demonstrated that both blood eosinophil percentage and the improved E - M score (subtraction of ethmoid and maxillary sinus scores) were significant predictors of ECRS diagnosis (P < .01). ROC curve analysis indicated that the combination of improved E - M score and blood eosinophil percentage had a higher diagnostic value compared to either factor alone (area under the curve = 0.874). Conclusion: Our study suggested the combination of improved total ethmoid sinus-maxillary score and blood eosinophil percentage is more accurate in predicting the diagnosis of ECRS.

Cisplatin attenuates taste cell homeostasis and induces inflammatory activation in the circumvallate papilla.

Rationale: Gustation is important to several biological functions in mammals. However, chemotherapy drugs often harm taste perception in cancer patients, while the underlying mechanism is still unclear for most drugs and there is no effective way to restore taste function. This study investigated the effects of cisplatin on the taste cell homeostasis and gustatory function. Methods: We used both mice and taste organoid models to study the effect of cisplatin on taste buds. Gustometer assay, gustatory nerve recording, RNA-Sequencing, quantitative PCR, and immunohistochemistry was performed to analyze the cisplatin-induced alteration in taste behavior and function, transcriptome, apoptosis, cell proliferation and taste cell generation. Results: Cisplatin inhibited proliferation and promoted apoptosis in the circumvallate papilla, leading to significant impairment in taste function and receptor cell generation. The transcriptional profile of genes associated with cell cycle, metabolic process and inflammatory response was significantly altered after cisplatin treatment. Cisplatin inhibited growth, promoted apoptosis, and deferred taste receptor cell differentiation in taste organoids. LY411575, a γ-secretase inhibitor, reduced the number of apoptotic cells and increased the number of proliferative cells and taste receptor cells, potentially suggesting as a taste tissue protective agent against chemotherapy. LY411575 treatment could offset the increased number of Pax1+ or Pycr1+ cells induced by cisplatin in the circumvallate papilla and taste organoids. Conclusion: This study highlights the inhibitory effects of cisplatin on taste cell homeostasis and function, identifies critical genes and biological processes regulated by chemotherapy, and proposes potential therapeutic targets and strategy for taste dysfunction in cancer patients.

Regulatory Role of miRNAs and lncRNAs in Gout.

Objective: To explore the regulatory functions of ceRNA networks in the nosogenesis of gout and search for potential therapeutic targets. Methods: We searched the GEO database and downloaded the lncRNA microarray chipset GSE160170. This matrix series was analyzed to yield differentially expressed lncRNAs and mRNAs. Then, the correlations between lncRNAs and miRNAs were obtained by comparing the highly conserved miRNA families. The predicted miRNA-regulating mRNAs were matched to the differentially expressed mRNAs from the chipset analyses to obtain miRNA-mRNA interactions. Next, we used the Cytoscape software to model ceRNA networks and the STRING database to determine their protein-protein interactions. The R software was used to algorithmically screen the functional pathways of key PPI modules in the ceRNA networks. Results: A total of 354 lncRNAs (140 downregulated and 214 upregulated) and 693 mRNAs (399 downregulated and 294 upregulated) were differentially expressed between the gout group and the healthy group. The ceRNA network of differentially expressed lncRNAs contained 86 lncRNAs (35 downregulated and 51 upregulated), 29 miRNAs, and 57 mRNAs. The processes identified in the GO enrichment analysis included gene transcription, RNA polymerase II transcription, and the regulation of cell growth and apoptosis. The pathways identified in the KEGG enrichment analysis included IL-17, TNF, and MAPK signaling. Nine lncRNAs (AC104024, AC084082, AC083843, FAM182A, AC022819, FAM215B, AP000525, TTTY10, and ZNF346-IT1), eleven miRNAs (hsa-miR-1297, hsa-miR-17-5p, hsa-miR-429, hsa-miR-139-5p, hsa-miR-449c-5p, hsa-miR-125a-5p, hsa-miR-125b-5p, hsa-miR-23b-3p, hsa-miR-217, hsa-miR-363-3p, and hsa-miR-20b-5p), and nine mRNAs (JUN, CASP2, PMAIP1, FOS, TNFAIP3, MAP3K8, BTG2, NR4A2, and DUSP2) were identified in the exploration of the key modules. Conclusion: Characterization of ceRNA networks could be a promising approach for better understanding the pathogenesis of gout, with the TTTY10/hsa-miR-139-5p/AP-1 axis likely to be of clinical significance.

Circular RNA hsa_circ_0102231 sponges miR-145 to promote non-small cell lung cancer cell proliferation by up-regulating the expression of RBBP4.

Circular RNAs (circRNAs) are important regulators in various cancers. Previous studies have found that hsa_circ_0102231 is an oncogene in lung adenocarcinoma. Here, we investigated its mechanism in the development of non-small cell lung cancer (NSCLC). We detected the levels of hsa_circ_0102231 in five NSCLC cell lines and one normal bronchial epithelium cell line. The interaction between hsa_circ_0102231 and miR-145 was predicted and confirmed by pull-down and luciferase assays. The nuclear mass separation assay and fluorescence in situ hybridization were used to detect the distribution of hsa_circ_0102231. Cell Counting Kit-8 and Transwell assays were used to assess the cell proliferative and invasive ability. Western blot and RT-qPCR, respectively, detected the protein and mRNA levels of RBBP4. The RBBP4 promoter activity was detected with a luciferase assay. We found that hsa_circ_0102231 level was higher in NSCLC cells. hsa_circ_0102231 is mainly localized to the cytoplasm. hsa_circ_0102231 promotes NSCLC cell proliferation and invasion by sponge for miR-145. miR-145 significantly decreases the RBBP4 promoter activity, and its mRNA and protein levels. RBBP4 is an oncogene to promote proliferation and invasion ability. Our findings suggest that hsa_circ_0102231 promotes proliferation and invasion by mediating the miR-145/RBBP4 axis in NSCLC, indicating that it might be a potential target for NSCLC treatment.