Purpose To investigate the clinicopathological characteristics,immunophenotype,high-risk human papillomavirus(hrHPV)infection status,treatment,and prognosis of cervical carcinoma exhibiting adenoid cystic car-cinoma(ACC)features.Methods Clinical data from 10 cases of cervical cancer with ACC features were collected.A retrospective analysis was proformed on the patients'clinicopathological data,histological features,and immunopheno-type(EnVision method),along with in situ hybridization detection of hrHPV E6/E7 mRNA covering 18 hrHPV types.Results The median age of the patients was 67.5 years,comprising 4 biopsy specimens and 6 surgical specimens.Except for 2 cases detected incidentally during physical examination,the remaining 8 cases presented with unexplained vaginal bleeding or contact bleeding.The mean tumor diameter was 4.5 cm(range:2.5 to 9.0 cm),and tumor stages were available for 8 patients(5 cases in stage Ⅰ and 1 case each in stages Ⅱ,Ⅲ,and Ⅳ).The follow-up period was 8 to 42 months,excluding 1 case lost to follow-up,2 cases(Ⅲ C1 and ⅣB)died within 1 year after surgery.Histologi-cally,4 cases exhibited pure ACC morphology,while 5 cases were mixed carcinomas(combined with squamous cell carcinoma,adenoid basal cell carcinoma,high-grade neuroendocrine carcinoma,or carcinosarcoma,respectively).The characteristic ACC morphology manifested as cribriform,pseudo-glandular,tubular,trabecular,and/or solid pat-terns with one case mixed carcinoma's lymph node metastasis showing only ACC morphology.Immunohistochemically,all 10 tumors exhibited diffuse strong positivity for p16 and p63,a high Ki67 proliferation index(40％to 90％),and wild-type p53 expression,and in 50％of cases,only a minority of cells were positive for c-MYB.Additionally,SOX10 was positive in 8 of 9 cases and CD117 was positive in 7 of 10 cases,respectively.In situ hybridization for hrHPV E6/E7 mRNA confirmed the presence of transcriptionally active HPV infection in all cases.Conclusion Cervical cancer with ACC features is rare,and predominantly occurs in postmenopausal elderly women.It represents an HPV-associat-ed high-grade carcinoma in which clinical stage is a critical prognostic factor.Immunohistochemical staining for CD117 and SOX10 aids in the pathological diagnosis of this tumor type.

Objective:To explore the chain mediating role of psychological resilience and perceived social support between cancer-related fatigue and quality of life in patients undergoing chemotherapy for lung cancer, and to inform interventions to improve quality of life in patients undergoing chemotherapy for lung cancer.Methods:Convenience sampling was used to select 275 lung cancer patients with chemotherapy admitted to three ClassⅢ Grade A hospitals in Henan Province from June 2022 to November 2023 for the study. General Information Questionnaire, Cancer Fatigue Scale, Quality of Life Instruments for Cancer Patients-Lung (QLICP-LU), Connor-Davidson Resilience Scale, and Perceived Social Support Scale were used to survey the patients. Correlations between cancer-related fatigue, psychological resilience, perceived social support, and quality of life in lung cancer patients with chemotherapy were analyzed using Spearman correlation. Model 6 in the SPSS PROCESS program was used to test for chain mediating effects. A total of 275 questionnaires were distributed, 268 questionnaires were recovered, excluding the regular answer questionnaires, the valid questionnaires were 252, the effective recovery rate of questionnaires was 91.64% (252/275) .Results:Univariate analysis showed statistically significant differences in QLICP-LU scores among lung cancer patients with chemotherapy of different ages, educational levels, marital status, per capita monthly household income, and tumor stages ( P<0.01). Spearman correlation analysis showed that cancer-related fatigue was negatively correlated with psychological resilience, perceived social support and quality of life in patients undergoing chemotherapy for lung cancer ( P<0.01), and quality of life was positively correlated with psychological resilience and perceived social support ( P<0.01), and psychological resilience was positively correlated with perceived social support ( P<0.01). Mediating effect analysis showed that the direct effect of cancer-related fatigue on quality of life was -0.302, which accounted for 77.44% of the total effect. Psychological resilience and perceived social support realized mediating effects between cancer-related fatigue and quality of life through three mediating pathways, with a total indirect effect of -0.088, accounting for 22.56% of the total effect. Conclusions:Cancer-related fatigue can not only directly affect the quality of life of patients undergoing chemotherapy for lung cancer, but it can also have an indirect effect on them through the mediating role of psychological resilience and perceived social support. While focusing on patients' cancer-related fatigue, medical and nursing staff should focus on assessing patients' psychological status, providing psychological support, and increasing social support so as to improve patients' quality of life.

Purpose To investigate the clinicopathological characteristics,immunophenotype,high-risk human papillomavirus(hrHPV)infection status,treatment,and prognosis of cervical carcinoma exhibiting adenoid cystic car-cinoma(ACC)features.Methods Clinical data from 10 cases of cervical cancer with ACC features were collected.A retrospective analysis was proformed on the patients'clinicopathological data,histological features,and immunopheno-type(EnVision method),along with in situ hybridization detection of hrHPV E6/E7 mRNA covering 18 hrHPV types.Results The median age of the patients was 67.5 years,comprising 4 biopsy specimens and 6 surgical specimens.Except for 2 cases detected incidentally during physical examination,the remaining 8 cases presented with unexplained vaginal bleeding or contact bleeding.The mean tumor diameter was 4.5 cm(range:2.5 to 9.0 cm),and tumor stages were available for 8 patients(5 cases in stage Ⅰ and 1 case each in stages Ⅱ,Ⅲ,and Ⅳ).The follow-up period was 8 to 42 months,excluding 1 case lost to follow-up,2 cases(Ⅲ C1 and ⅣB)died within 1 year after surgery.Histologi-cally,4 cases exhibited pure ACC morphology,while 5 cases were mixed carcinomas(combined with squamous cell carcinoma,adenoid basal cell carcinoma,high-grade neuroendocrine carcinoma,or carcinosarcoma,respectively).The characteristic ACC morphology manifested as cribriform,pseudo-glandular,tubular,trabecular,and/or solid pat-terns with one case mixed carcinoma's lymph node metastasis showing only ACC morphology.Immunohistochemically,all 10 tumors exhibited diffuse strong positivity for p16 and p63,a high Ki67 proliferation index(40％to 90％),and wild-type p53 expression,and in 50％of cases,only a minority of cells were positive for c-MYB.Additionally,SOX10 was positive in 8 of 9 cases and CD117 was positive in 7 of 10 cases,respectively.In situ hybridization for hrHPV E6/E7 mRNA confirmed the presence of transcriptionally active HPV infection in all cases.Conclusion Cervical cancer with ACC features is rare,and predominantly occurs in postmenopausal elderly women.It represents an HPV-associat-ed high-grade carcinoma in which clinical stage is a critical prognostic factor.Immunohistochemical staining for CD117 and SOX10 aids in the pathological diagnosis of this tumor type.

Objective:To explore the chain mediating role of psychological resilience and perceived social support between cancer-related fatigue and quality of life in patients undergoing chemotherapy for lung cancer, and to inform interventions to improve quality of life in patients undergoing chemotherapy for lung cancer.Methods:Convenience sampling was used to select 275 lung cancer patients with chemotherapy admitted to three ClassⅢ Grade A hospitals in Henan Province from June 2022 to November 2023 for the study. General Information Questionnaire, Cancer Fatigue Scale, Quality of Life Instruments for Cancer Patients-Lung (QLICP-LU), Connor-Davidson Resilience Scale, and Perceived Social Support Scale were used to survey the patients. Correlations between cancer-related fatigue, psychological resilience, perceived social support, and quality of life in lung cancer patients with chemotherapy were analyzed using Spearman correlation. Model 6 in the SPSS PROCESS program was used to test for chain mediating effects. A total of 275 questionnaires were distributed, 268 questionnaires were recovered, excluding the regular answer questionnaires, the valid questionnaires were 252, the effective recovery rate of questionnaires was 91.64% (252/275) .Results:Univariate analysis showed statistically significant differences in QLICP-LU scores among lung cancer patients with chemotherapy of different ages, educational levels, marital status, per capita monthly household income, and tumor stages ( P<0.01). Spearman correlation analysis showed that cancer-related fatigue was negatively correlated with psychological resilience, perceived social support and quality of life in patients undergoing chemotherapy for lung cancer ( P<0.01), and quality of life was positively correlated with psychological resilience and perceived social support ( P<0.01), and psychological resilience was positively correlated with perceived social support ( P<0.01). Mediating effect analysis showed that the direct effect of cancer-related fatigue on quality of life was -0.302, which accounted for 77.44% of the total effect. Psychological resilience and perceived social support realized mediating effects between cancer-related fatigue and quality of life through three mediating pathways, with a total indirect effect of -0.088, accounting for 22.56% of the total effect. Conclusions:Cancer-related fatigue can not only directly affect the quality of life of patients undergoing chemotherapy for lung cancer, but it can also have an indirect effect on them through the mediating role of psychological resilience and perceived social support. While focusing on patients' cancer-related fatigue, medical and nursing staff should focus on assessing patients' psychological status, providing psychological support, and increasing social support so as to improve patients' quality of life.

Background and Aims:Carotid plaque instability is a critical pathological basis for ischemic stroke.Identifying key molecular markers to evaluate plaque stability has important clinical implications.Recent studies have emphasized the regulatory roles and predictive value of long non-coding RNAs(lncRNAs)in plaque stability.In our previous transcriptome sequencing analysis of human stable and unstable carotid plaques,we identified lncRNA C-C motif chemokine ligand 3 antisense RNA 1(CCL3-AS1)as significantly upregulated in unstable plaques,suggesting a potential association with plaque instability.Therefore,this study aimed to validate CCL3-AS1 expression in an expanded plaque sample cohort and to explore its role and underlying molecular mechanism in carotid plaque destabilization.Methods:Carotid plaque specimens were obtained from patients undergoing carotid endarterectomy and classified into stable and unstable groups(n=15 per group)based on HE and Sirius red staining.qRT-PCR was used to validate the expression of candidate lncRNA CCL3-AS1.The localization and co-expression of CCL3-AS1 with macrophages in plaques were determined by RNA fluorescence in situ hybridization(FISH)combined with immunofluorescence staining.In vitro,THP1-derived macrophages were transduced with lentivirus or treated with antisense oligonucleotides(ASO)to overexpress or knock down CCL3-AS1,respectively,and the expression levels of inflammatory cytokines and matrix metalloproteinases(MMPs)were assessed.In vivo,an unstable carotid plaque model was established by tandem ligation of the right carotid artery in apolipoprotein E-deficient(ApoE-/-)mice,followed by local overexpression of CCL3-AS1.The effects on plaque morphology,macrophage infiltration,and MMP-9 expression were evaluated.Additionally,bioinformatic prediction using the catRAPID v2.1 omics platform was performed to identify potential RNA-binding proteins interacting with CCL3-AS1.RNA stability assays and RNA-binding protein immunoprecipitation(RIP)were conducted to verify the regulatory mechanism of MMP-9 expression.Results:CCL3-AS1 was significantly upregulated in unstable carotid plaques and was predominantly localized to the cytoplasm of plaque-infiltrating macrophages.In vitro,overexpression of CCL3-AS1 markedly increased the expression of MCP-1,TNF-α,IL-1β,iNOS,and MMP-9 in macrophages,whereas knockdown had the opposite effect.In the ApoE-/-mouse model of unstable carotid plaques,CCL3-AS1 overexpression led to fibrous cap rupture,increased infiltration of pro-inflammatory macrophages,enhanced MMP-9 secretion,and promoted plaque instability.Co-expression analysis revealed a strong correlation between CCL3-AS1 and MMP-9 expression(r=0.89,P=0.001).RNA stability assays demonstrated that CCL3-AS1 delayed the degradation of MMP-9 mRNA.Bioinformatic prediction identified heterogeneous nuclear ribonucleoprotein K(hnRNP-K)as a potential binding partner of CCL3-AS1.RIP and FISH co-localization confirmed the interaction,suggesting that CCL3-AS1 enhances MMP-9 mRNA stability through binding to hnRNP-K,thereby promoting its expression.Conclusion:As a macrophage-enriched inflammatory lncRNA,CCL3-AS1 may promote carotid plaque instability by enhancing MMP-9 expression via hnRNP-K-mediated mRNA stabilization.This lncRNA represents a potential molecular target for early intervention and stratification of ischemic stroke.

Objective To analyze the factors affecting the prevalence of hyperuricemia(HUA)in an island troop.Methods A total of 1 113 soldiers stationed on an island from December 2021 to December 2022 were selected as research objects by cluster sampling.Their lifestyle and health information were collected.Physical examination and laboratory detection were conducted.Multivariate logistic regression was used to analyze the influencing factors of HUA.Results The prevalence rate of HUA was 21.02%(234/1 113).There were significant differences in the body mass index(BMI),waist-to-hip ratio,triglyceride,alanine aminotransferase,and creatinine between the soldiers with hyperuricemia and the soldiers with normal blood uric acid(P<0.05).Multivariate logistic regression analysis showed that BMI≥24(OR=1.49,95%CI:1.09-2.05),abnormal liver function(OR=2.26,95%CI:1.31-3.92),and dyslipidemia(OR=1.46,95%CI:1.01-2.12)were positively correlated with hyperuricemia;age>30 years old(OR=0.59,95%CI:0.37-0.93)and exercise time>1 h per week(OR=0.46,95%CI:0.22-0.97)were negatively correlated with HUA.Conclusion The prevalence rate of hyperuricemia is at a high level in an island troop.BMI≥24,age≤30 years old,exercise time≤1 h per week,abnormal liver function,and dyslipidemia are the risk factors for HUA.Prevention and control measures should be taken as early as possible for the soldiers with these risk factors.

G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

Background and Aims:Carotid plaque instability is a critical pathological basis for ischemic stroke.Identifying key molecular markers to evaluate plaque stability has important clinical implications.Recent studies have emphasized the regulatory roles and predictive value of long non-coding RNAs(lncRNAs)in plaque stability.In our previous transcriptome sequencing analysis of human stable and unstable carotid plaques,we identified lncRNA C-C motif chemokine ligand 3 antisense RNA 1(CCL3-AS1)as significantly upregulated in unstable plaques,suggesting a potential association with plaque instability.Therefore,this study aimed to validate CCL3-AS1 expression in an expanded plaque sample cohort and to explore its role and underlying molecular mechanism in carotid plaque destabilization.Methods:Carotid plaque specimens were obtained from patients undergoing carotid endarterectomy and classified into stable and unstable groups(n=15 per group)based on HE and Sirius red staining.qRT-PCR was used to validate the expression of candidate lncRNA CCL3-AS1.The localization and co-expression of CCL3-AS1 with macrophages in plaques were determined by RNA fluorescence in situ hybridization(FISH)combined with immunofluorescence staining.In vitro,THP1-derived macrophages were transduced with lentivirus or treated with antisense oligonucleotides(ASO)to overexpress or knock down CCL3-AS1,respectively,and the expression levels of inflammatory cytokines and matrix metalloproteinases(MMPs)were assessed.In vivo,an unstable carotid plaque model was established by tandem ligation of the right carotid artery in apolipoprotein E-deficient(ApoE-/-)mice,followed by local overexpression of CCL3-AS1.The effects on plaque morphology,macrophage infiltration,and MMP-9 expression were evaluated.Additionally,bioinformatic prediction using the catRAPID v2.1 omics platform was performed to identify potential RNA-binding proteins interacting with CCL3-AS1.RNA stability assays and RNA-binding protein immunoprecipitation(RIP)were conducted to verify the regulatory mechanism of MMP-9 expression.Results:CCL3-AS1 was significantly upregulated in unstable carotid plaques and was predominantly localized to the cytoplasm of plaque-infiltrating macrophages.In vitro,overexpression of CCL3-AS1 markedly increased the expression of MCP-1,TNF-α,IL-1β,iNOS,and MMP-9 in macrophages,whereas knockdown had the opposite effect.In the ApoE-/-mouse model of unstable carotid plaques,CCL3-AS1 overexpression led to fibrous cap rupture,increased infiltration of pro-inflammatory macrophages,enhanced MMP-9 secretion,and promoted plaque instability.Co-expression analysis revealed a strong correlation between CCL3-AS1 and MMP-9 expression(r=0.89,P=0.001).RNA stability assays demonstrated that CCL3-AS1 delayed the degradation of MMP-9 mRNA.Bioinformatic prediction identified heterogeneous nuclear ribonucleoprotein K(hnRNP-K)as a potential binding partner of CCL3-AS1.RIP and FISH co-localization confirmed the interaction,suggesting that CCL3-AS1 enhances MMP-9 mRNA stability through binding to hnRNP-K,thereby promoting its expression.Conclusion:As a macrophage-enriched inflammatory lncRNA,CCL3-AS1 may promote carotid plaque instability by enhancing MMP-9 expression via hnRNP-K-mediated mRNA stabilization.This lncRNA represents a potential molecular target for early intervention and stratification of ischemic stroke.

Objective:To explore the clinical effect of non-expansion whole framework ear reconstruction for microtia (referred to as the NEWF ear reconstruction).Methods:The clinical data of congenital microtia patients underwent NEWF ear reconstruction at Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. This advanced method used a tissue non-expansion approach, employing a double flap consisting of preauricular skin flap and fascia flaps, to fabricate and elevate the ear framework in the first stage concurrently. In the subsequent stage, residual ear tissues were utilized to reconstruct key elements such as the tragus, crus of the helix, cavum concha, and so on. At 6 months follow-up, the effectiveness of the reconstructed ear was assessed based on its aesthetic outcomes and complications. Aesthetic outcomes evaluation included 4 items: skin color (front of ear, back of ear and skin graft area were evaluated respectively), appearance of reconstructed ear substructure, scar of incision and hair condition. The individual score was 0-2 points, total scores from 0 to 10, with scores of 9-10 signifying excellent, 6-8 good, 3-5 moderate, and 0-2 poor. The data were analyzed by descriptive statistics.Results:Ear reconstruction was performed on 49 unilateral microtia cases, aged 6-33 years, including 37 males and 12 females, 34 right ears and 15 left ears. According to the Nagata classification: 30 cases were lobule-type, 5 cases were conchal-type, and 14 cases were small conchal-type. The follow-up period averaged 10.63 months, ranging from 6 to 13 months. One patient experienced exposure of the framework 1 month after the first stage surgery, then recovered well after surgery. The skin color of the front side of the reconstructed ear was close to normal, the substructure was clear, the skin graft area behind the ear recovered well, and the reconstructed ear was basically symmetrical with the healthy side. 9 cases (18.4%) had scar hyperplasia in the mastoid area behind the ear. 9 cases (18.4%) had hair growth on the front of the reconstructed ears. Aesthetic outcomes showed that excellent in 8 cases (16.3%), good in 36 cases (73.5%), moderate in 4 cases (8.2%), poor in 1 case (2.0%).Conclusion:The NEWF ear reconstruction enhances the stability of the ear framework, reduces the overall duration of treatment, making it a viable option for ear reconstruction for microtia.

Embryo implantation, as an important speed limiting step in pregnancy, is a dynamic developmental process that involves a series of intercellular communication and interactions between the embryo and endometrial cells. Exosomes are a subtype of extracellular vesicles that are widely present in cells and bodily fluids and can serve as new intercellular communication mediators in the body. Research has shown that exosomes can participate in regulating embryonic development, endometrial receptivity, embryo adhesion, immune tolerance, and angiogenesis, playing an important role in regulating complex embryo implantation processes. This article will review the role of exosomes in embryo implantation, in order to provide new insights into the failure of embryo implantation in human reproduction.