Objective:To investigate the molecular mechanism by which 2',4'-dihydroxychalcone(D2)inhibits proliferation,migration,and epithelial-mesenchymal transition(EMT)in colorectal cancer cells through miR-7-5p-mediated autophagy.Methods:Human colorectal cancer cell lines HCT-15 and SW620 were treated with D2 at concentrations of 0,12.5,25,and 50 μmol/L.Cell proliferation and clonogenic capacity were evaluated using MTT and colony formation assays.Cell migration was assessed by wound healing and Transwell assays.WB assay was used to detect the expression of EMT-related proteins,autophagy-related proteins,and key components of the PI3K/AKT/mTOR pathway.Autophagosome formation was visualized by immunofluorescence staining.TCGA database and KEGG pathway analyses were performed to evaluate miR-7-5p expression and its association with colorectal cancer.RT-qPCR was used to quantify miR-7-5p expression,and lentiviral transduction was employed to establish stable miR-7-5p knockdown or overexpression cell lines.Results:D2 significantly inhibited colorectal cancer cell proliferation,migration,and EMT(P<0.05 or P<0.01).TCGA and KEGG analyses revealed that miR-7-5p expression was downregulated in colorectal cancer and closely associated with disease progression.D2 treatment(12.5,25,and 50 μmol/L)significantly upregulated miR-7-5p expression in HCT-15 and SW620 cells(P<0.01).At 25 μmol/L,D2 increased the expression of autophagy-related proteins(LC3 and p-ULK1)and inhibited the PI3K/AKT/mTOR signaling pathway(P<0.05),accompanied by increased autophagosome formation(P<0.01).In miR-7-5p-knockdown cells treated with D2,the levels of LC3 and p-ULK1 were significantly reduced compared to D2-only treated cells(P<0.05 or P<0.01).Conclusion:D2 upregulates miR-7-5p to induce autophagy,thereby inhibiting colorectal cancer cell proliferation,migration,and EMT,possibly through suppression of the PI3K/AKT/mTOR signaling pathway.

Objective:To investigate the correlation of combined detection of p16 and Rb with high-risk human papilloma virus (HR-HPV) infection in non-oropharyngeal squamous cell carcinoma (NOPSCC) of the head and neck.Methods:A total of 68 NOPSCC cases of the head and neck (23 cases of the nasal cavity and paranasal sinuses and 45 cases of larynx) with complete clinical and pathological data, diagnosed at the Beijing Tongren Hospital, Capital Medical University, Beijing, China from November 2013 to December 2023, were collected. The expression of p16 and Rb was detected using immunohistochemistry of the EnVision two-step method, while the HR-HPV mRNA expression was detected using in situ hybridization. The concordance, sensitivity, and specificity of p16 alone and the combined detection of p16 and Rb for detecting HR-HPV infection were analyzed.Results:Among the 68 patients with NOPSCC, 53 were male and 15 were female, with a median age of 63.5 (range, 57.3 to 66.8) years. 41 patients had a smoking history and 27 did not. 33 patients had an early T stage (T1/T2) and 35 had advanced T stage (T3/T4). 14 patients had lymph node metastasis and 2 had distant metastasis. Histological types included 62 cases of keratinized squamous cell carcinoma, 5 cases of non-keratinized squamous cell carcinoma, and 1 case of basal-like squamous cell carcinoma. 25 cases were positive for p16. Among the 25 cases, 16 cases were positive for Rb, and 6 cases were positive for HR-HPV mRNA. 43 cases were negative for p16, including 38 cases positive for Rb and no cases positive for HR-HPV mRNA. The concordance between p16 and HR-HPV mRNA expression was poor ( Kappa=0.285, P=0.001), with a sensitivity of 100.0% and specificity of 69.4%. In contrast, the combined detection of p16+/Rb- showed high concordance with HR-HPV mRNA expression ( Kappa=0.719, P<0.001), with a sensitivity of 100.0% and specificity of 95.2%. Conclusions:In NOPSCC of the head and neck, the combined detection of p16 and Rb may be used as a marker for assessing HR-HPV infection. Recognizing the p16+/Rb- expression pattern in NOPSCC can improve the specificity of HR-HPV detection.

Objective:To investigate the correlation of combined detection of p16 and Rb with high-risk human papilloma virus (HR-HPV) infection in non-oropharyngeal squamous cell carcinoma (NOPSCC) of the head and neck.Methods:A total of 68 NOPSCC cases of the head and neck (23 cases of the nasal cavity and paranasal sinuses and 45 cases of larynx) with complete clinical and pathological data, diagnosed at the Beijing Tongren Hospital, Capital Medical University, Beijing, China from November 2013 to December 2023, were collected. The expression of p16 and Rb was detected using immunohistochemistry of the EnVision two-step method, while the HR-HPV mRNA expression was detected using in situ hybridization. The concordance, sensitivity, and specificity of p16 alone and the combined detection of p16 and Rb for detecting HR-HPV infection were analyzed.Results:Among the 68 patients with NOPSCC, 53 were male and 15 were female, with a median age of 63.5 (range, 57.3 to 66.8) years. 41 patients had a smoking history and 27 did not. 33 patients had an early T stage (T1/T2) and 35 had advanced T stage (T3/T4). 14 patients had lymph node metastasis and 2 had distant metastasis. Histological types included 62 cases of keratinized squamous cell carcinoma, 5 cases of non-keratinized squamous cell carcinoma, and 1 case of basal-like squamous cell carcinoma. 25 cases were positive for p16. Among the 25 cases, 16 cases were positive for Rb, and 6 cases were positive for HR-HPV mRNA. 43 cases were negative for p16, including 38 cases positive for Rb and no cases positive for HR-HPV mRNA. The concordance between p16 and HR-HPV mRNA expression was poor ( Kappa=0.285, P=0.001), with a sensitivity of 100.0% and specificity of 69.4%. In contrast, the combined detection of p16+/Rb- showed high concordance with HR-HPV mRNA expression ( Kappa=0.719, P<0.001), with a sensitivity of 100.0% and specificity of 95.2%. Conclusions:In NOPSCC of the head and neck, the combined detection of p16 and Rb may be used as a marker for assessing HR-HPV infection. Recognizing the p16+/Rb- expression pattern in NOPSCC can improve the specificity of HR-HPV detection.

Objective To investigate the effect of baicalein (BAI) on autophagy of gastric cancer cell line BGC-823 cells by upregulating microRNA-7-5p (miR-7) and its possible mechanism. Methods The MTT method was used to screen the optimal drug concentration of BGC-823 cells treated with BAI. Real-time quantitative PCR was used to detect the transfection efficiency of BGC-823 cell line stably transfected with miR-7. The experiment was divided into control group (mimic-NC), miR-7 group (miR-7 mimic) and BAI group ( miR-7 overexpression combined with BAI treatment group). MTT assay, plate cloning assay and EdU assay were used to detect cell proliferation. The expression levels of autophagy related 16 like 1 (ATG16L1), sequestosome 1 (p62), Beclin 1, autophagy-related protein 5 (ATG5) and microtubule-assaiated protein 1 light chain3 (LC3) were detected by immunofluorescence staining and Western blot. Network pharmacology analysis to predict possible signaling pathways; Western blot was used to detect the expression levels of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Results 50 μmol/L BAI significantly inhibited the proliferation ability of BGC-823 cells; Compared with the control group, the expression level of miR-7 was significantly increased after BAI treatment. The cell proliferation of the miR-7 group was significantly inhibited, and the protein expression level of autophagy-related proteins and the LC3II/LC3I ratio were significantly up-regulated, which promoted the formation of autophagosomes and inhibited the formation of autophagic flow in BGC-823 cells. Compared with the miR-7 group, the BAI group could further inhibit the proliferation of BGC-823 cells, induce the formation of autophagosomes, but inhibit the production of autophagy flow. Network pharmacology analysis showed that the common target genes of BAI, gastric cancer and autophagy may be related to PI3K/AKT signaling pathway. Compared with the control group, the phosphorylation levels of p-PI3K, p-AKT and p-mTOR in the miR-7 group were significantly inhibited, and the phosphorylation levels of these proteins were further inhibited in the BAI group. Conclusion BAI-mediated miR-7 inhibits the formation of autophagosomes in BGC-823 cells by inhibiting PI3K/AKT/mTOR signaling pathway, and inhibits the generation of autophagic flow.
Humans ; MicroRNAs/metabolism* ; Stomach Neoplasms/drug therapy* ; Autophagy/genetics* ; Cell Line, Tumor ; Flavanones/pharmacology* ; Cell Proliferation/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/genetics* ; Gene Expression Regulation, Neoplastic/drug effects*

OBJECTIVE To analyze the differences in clinical and imaging characteristics of patients with respiratory epithelial adenomatoid hamatoma(REAH)and nasal polyps(NP)whose lesions are located in bilateral olfactory cleft regions,so as to provide evidence for clinicians in the preoperative differential diagnosis of REAH and NP.METHODS Patients with bilateral olfactory cleft REAH,who underwent nasal endoscopic surgery from June 2006 to August 2023 in Beijing Tongren Hospital,were retrospectively analyzed as the REAH group.Patients with bilateral olfactory cleft NP who underwent nasal endoscopic surgery from January 2023 to October 2023 in Beijing Tongren Hospital were included and set as the NP group.The demographic and clinical characteristics,as well as the sinus CT data were analyzed to explore the intergroup differences.RESULTS Both the REAH group and the NP group included 155 patients.The REAH group was dominated by older men,and the prevalence of comorbid asthma was lower than that in the NP group(P<0.05).In the REAH group,the middle turbinate width,the superior turbinate width,the ratio of middle turbinate width/orbital board width,the ratio of superior turbinate width/middle orbital board width,and the maximum angle between the middle turbinate and nasal septum were significantly higher than those in the NP group(P<0.05).CONCLUSION Sinus CT examination can help clinicians identify REAH lesions before surgery,which is conducive to the formulation and implementation of treatment plans.

OBJECTIVE To investigate the diagnostic value of BRAFV600E gene detection for the benign and malignant nature of TBSRTC categories Ⅰ and Ⅱ thyroid nodules.METHODS Cases with ultrasound-guided fine-needle aspiration cytology(FNAC)results of TBSRTC categories Ⅰ and Ⅱ thyroid nodules with concomitant BRAFV600E gene detection results were retrospectively collected from August 2021 to June 2024 in Beijing Tongren Hospital,Capital Medical University(176 patients with 182 nodules in category Ⅰ,492 patients with 503 nodules in category Ⅱ).The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of BRAFV600E gene detection on the benign and malignant nature of TBSRTC categories Ⅰ and Ⅱ thyroid nodules were analyzed using nodules with surgical histopathological results as the'gold standard'(26 category Ⅰ and 37 category Ⅱ nodules).RESULTS Twenty-two of the 26 category Ⅰ nodules were papillary thyroid carcinoma(PTC)and 4 were benign lesions;18 of the 37 category Ⅱ nodules were PTC and 19 were benign lesions.The sensitivities of BRAFV600E gene detection on the benign and malignant nature of TBSRTC categories Ⅰ and Ⅱ thyroid nodules were 100％(22/22)and 83.3％(15/18),the specificities were 100％(4/4)and 94.7％(18/19),the positive predictive values were 100％(22/22)and 93.7％(15/16),the negative predictive values were 100％(4/4)and 85.7％(18/21),and the accuracy rates were 100％(26/26)and 89.2％(33/37).There was a 0％(0/3)concordance of FNAC results for the 3 thyroid nodules with repeat puncture and a 100％(1/1)concordance of BRAFV600E gene detection results.CONCLUSION BRAFV600E gene detection is an effective diagnostic method for the differentiation of benign and malignant nature of TBSRTC categories Ⅰ and Ⅱ thyroid nodules.In addition to BRAFV600E gene detection for TBSRTC categories Ⅲ-Ⅴ nodules,it is recommended that TBSRTC categories Ⅰ and Ⅱ nodules also be included in routine BRAFV600E gene detection to minimize the need for repeat puncture in patients and to reduce the rate of missed diagnosis of PTC.

Objective:To investigate the genomic profiles and immune microenvironment of olfactory neuroblastoma (ONB).Methods:Nineteen ONB cases diagnosed in the Beijing Tongren Hospital from May 2018 to October 2022 were divided into low-grade and high-grade groups according to the Hyams grading system, including 7 low-grade and 12 high-grade ONB. Whole exome sequencing and multiplex immunofluorescence analyses were performed on tissue samples of these ONB.Results:A total of 929 nonsynonymous alterations were identified in 18 of the 19 ONB (18/19) cases. The most commonly altered cancer-related genes were CTNNB1 (3/19) and ZNRF3 (3/19). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45/Mb, ranging from 0 to 3.25. The median tumor neoantigen load (TNB) was 9.39 neoantigens/Mb, ranging from 0 to 38.30. The median allelic mutation tumor heterogeneity (MATH) score was 16.95, ranging from 3.05 to 117.47. Only one of the 19 cases expressed PD-L1 (composite positive score, CPS>1) in the tumor cells. The median percentage of CD8 + tumor-infiltrating lymphocyte (TIL) in the tumor region was 1.08%. No significant differences were observed between the low-and high-grade groups for mutant genes, mutant pathways, TMB, TNB, MATH, PD-L1 expression levels, or CD8 + TILs percentage( P>0.05). However, the low-grade group showed significantly more CD68 + macrophages in both the tumor and total region than the high-grade group. Notably, CD68 +CD163 - macrophages accounted for an average of 80.52% of CD68 + macrophages. Conclusions:CTNNB1 and ZNRF3 are the most commonly altered cancer-related genes. The low expression of PD-L1 and the low percentage of CD8 + TIL indicate that ONB might not be sensitive to immunotherapy. The percentage of M1-type macrophages in low-grade ONB is significantly higher than that in high-grade ONB, suggesting that M1-type macrophages may be involved in the progression of ONB from low-grade to high-grade.

BACKGROUND: To compare the efficacy and safety of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Waldeyer's ring diffuse large B-cell lymphoma (WR-DLBCL) at a single institution. METHODS: This retrospective study included 115 newly diagnosed patients with WR-DLBCL, of whom 68 patients received R-CHOP, and 47 patients received DA-EPOCH-R as their first-line treatment. The baseline features of the two groups were well balanced using a 1:1 propensity score matching method, and a total of 84 cases were obtained, including respective 42 cases in the R-CHOP and DA-EPOCH-R groups, for further survival and prognosis analysis. The primary objectives included progression-free survival (PFS) and overall survival (OS). RESULTS: During a median follow-up of 45 months, there were nine (21.4%) deaths in the R-CHOP group and two (4.8%) in the DA-EPOCH-R group. Kaplan-Meier analysis showed statistically significant improvements in PFS and OS in patients with DA-EPOCH-R compared with those treated with R-CHOP (log-rank test, P  = 0.025 and P  = 0.035, respectively). The 2-year PFS and OS rates in the DA-EPOCH-R group were 90.1% (95% confidence interval [CI]: 81.4-99.8%) and 95.2% (95% CI: 89.0-100.0%), respectively, and 80.5% (95% CI: 69.3-93.6%) and 90.5% (95% CI: 52.8-99.8%) in the R-CHOP group. Patients without B symptoms and elevated lactate dehydrogenase levels had a higher PFS in the DA-EPOCH-R group, with P values of 0.038 (hazard ratio [HR]: 0.11; 95% CI: 0.01-0.88) and 0.042 (HR: 0.19; 95% CI: 0.04-0.94), respectively. There were no statistically significant differences in clinical responses and treatment-related toxicities between the two groups. CONCLUSION Compared with patients received R-CHOP, those treated by DA-EPOCH-R had superior PFS, OS, and controlled toxicity in patients with WR-DLBCL.
Humans ; Rituximab/therapeutic use* ; Vincristine/therapeutic use* ; Retrospective Studies ; Prednisone/therapeutic use* ; Etoposide/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Cyclophosphamide/therapeutic use* ; Doxorubicin/therapeutic use*

Objective:To study clinicopathological features and differential diagnosis of IgG4-related diseases (IgG4-RD) in nasal cavity and paranasal sinuses.Methods:A retrospective analysis was performed in patients presenting initially with rhinosinusitis or a nasal mass, who also underwent nasal mucosa biopsy in Beijing Tongren Hospital Affiliated to Capital Medical University, from March 2016 to March 2021. According to the latest international classification diagnostic criteria of IgG4-RD published by the American Society of Rheumatology (ACR)/European Association for Rheumatology (EULAR) in 2019, 10 cases of nasal cavity and paranasal sinuses IgG4-RD were diagnosed and included in the study. The clinical features, histopathology and immunohistochemical expression of IgG and IgG4 were analyzed.Results:Among the 10 patients, five patients were male and five female. The age ranged from 30 to 71 years (median 52.7 years). Nasal polyp/nasal masses were seen in six cases, and lacrimal gland swelling was found in four cases. The serum IgG and IgG4 level was increased in four cases. Microscopically, all 10 cases showed intense lymphoplasmocytic infiltration and varying degrees of fibrosis in nasal or sinus mucosa, while four cases showed occlusive vasculitis. The number of IgG4 positive plasma cells in nasal mucosa was more than 10/high power field (HPF), with a mean of 67/HPF. The number of IgG4 positive plasma cells in the cases with severe fibrosis was significantly lower than in those without. The ratio of IgG4 +/IgG +plasma cells was higher than 40% in six cases. Conclusions:IgG4-RD in nasal cavity and paranasal sinuses is a local manifestation of a systemic disease, while nasal cavity and paranasal sinuses are rarely involved by IgG4-RD. The diagnosis is based on clinical symptoms, imaging, IgG4-related serology and histopathologic scores. Histopathology has a core diagnostic value. IgG4 serology and imaging have important diagnostic values in the cases without biopsy.

Objective:To evaluate the CT characteristics of ossifying foci in sinonasal inverted papilloma (IP) and to compare with the tumor root shown intraoperatively.Methods:The clinical and CT imaging data of 127 patients with IP, which were proved by histopathology, were reviewed retrospectively from Beijing Tongren Hospital, Capital Medical University, during the period from January 2012 to December 2018. The number, location, shape, density of ossifying foci in sinonasal IP and the relationship with the wall of sinus were observed. The sites of ossification on CT scans were compared with the root of the tumors described in the corresponding patient′s operative records.Results:In 127 IP patients, 51 (40.2%) patients showed the ossification in the tumor on CT. Single ossifying foci were found in 35 cases and multiple in 16 cases. The ossification affected single site of the sinonasal tract ( n=16) or distributed diffusely ( n=35). In the 50 cases, the ossifying foci extended along the long axis of the affected sinus appearing as branched ( n=19), striped ( n=16), linear ( n=7), lumpy ( n=2) or mixed type ( n=6), and 1 case was located at the edge of the maxillary sinus. Totally 66.7% (34/51) of the ossifying focis contained peripherally hyperdense bone tissue and centrally hypodense adipose tissue, which corresponded to bone cortices and fatty marrow of the trabecular bone. And 96.1% (49/51) of the ossifying focis were attached to the adjacent bone of the sinus, and the sites of attachment were concordant with the actual origin of tumor confirmed in operation . Conclusions:Ossification can be seen in some sinonasal IPs. Tracing along ossifying focus to the site of attachment with sinus might facilitate preoperative prediction of the originating site of tumor.