Background Thyroid hormones are crucial for development and proper functioning of human physiological systems. Current research on the thyroid mainly focuses on the impacts of lifestyle factors on thyroid dysfunction, while less attention is paid to the factors affecting thyroid hormone levels, especially occupational hazards, which warrants further investigation. Objective To investigate the associations between occupational hazard exposure and thyroid-stimulating hormone (TSH) and thyroid hormone levels in male coal mine workers. Methods A cross-sectional study design was adopted. A total of 12564 workers who participated in the occupational health check-ups at the Xishan Coal Electricity (Group) Corporation Occupational Disease Prevention and Control Institute in 2023 and met the inclusion and exclusion criteria were selected as research subjects. A self-designed electronic questionnaire was used to collect basic information, occupational history, and lifestyle habits of all study subjects. Height, weight, thyroid function test results, and occupational hazard exposure of the study subjects were obtained through occupational health examinations and routine workplace occupational hazard detection records. Generalized linear regression was used to analyze the associations between occupational hazard exposure and the levels of TSH and thyroid hormones. Results The median (P₂₅, P₇₅) levels of triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), and TSH in the included 12564 male coal mine workers were 1.16 (1.03, 1.29) ng·mL⁻¹, 7.70 (6.70, 8.90) μg·dL⁻¹, 3.63 (3.40, 3.84) pg·mL⁻¹, 1.19 (1.08, 1.30) ng·dL⁻¹, and 1.93 (1.36, 2.78) μIU·mL⁻¹, respectively. The overall abnormality rate of thyroid hormones was 2.83%, with the highest rate for subclinical hypothyroidism (1.83%), followed by hyperthyroidism (0.37%), hypothyroidism (0.32%), and subclinical hyperthyroidism (0.31%). After adjustment for confounding factors, the generalized linear regression model showed that long working hours were associated with higher levels of T3 and FT3, with β (95%CI) values of 0.011 (0.003, 0.019) and 0.038 (0.019, 0.057) respectively. Night shift work was linked to increased TSH levels and decreased FT4 levels, with β (95%CI) values of 0.171 (0.016, 0.326) and −0.012 (−0.019, −0.006) respectively. Coal dust exposure was associated with decreased levels of T3 and T4, with β (95%CI) values of −0.022 (−0.037, −0.008) and −0.320 (−0.434, −0.207) respectively. Noise exposure was related to decreased levels of T4 and FT4, with β (95%CI) values of −0.102 (−0.166, −0.038) and −0.020 (−0.027, −0.013) respectively. Conclusion The TSH and thyroid hormone levels of coal miners are mostly within the normal reference ranges, with a low abnormality rate. Long work hours, night shift work, coal dust, and noise are associated with the levels of TSH and thyroid hormone levels in the male miners. Coal companies should reasonably arrange working hours, optimize the night shift scheduling system, and enhance protection against coal dust and noise to promote occupational health and safeguard the physical health of miners.

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 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.

Objective To establish a model of long-term atrazine(ATR)-induced liver injury in mice and to evaluate the hepatotoxic effects induced by ATR.Methods C57BL/6-N male mice were randomly divided into a control group and 1.5 mg/L and 150 mg/L ATR dose(ATR-L,ATR-H)groups.After 35 and 63 days,serum liver function biochemical indexes and inflammatory factors were detected,the hepatosomatic ratio was calculated,and the histopathology and ultrastructure of the liver were observed.Lipid peroxidation levels and antioxidant capacity,the activities of major phase I metabolic enzymes and phase Ⅱ detoxification enzymes,and the expression of related proteins in liver tissues were detected.Results Compared with the control group,the ATR groups showed significant changes in the AST/ALT ratio,levels of pro-inflammatory factors CCL2,TNF-α and IL-6,H2O2 content and activities of the metabolic enzymes NCR,CYTb5,and UDPGT(P＜0.05).In the 150 mg/L ATR group,GGT content,peroxide levels(as indicated by malondialdehyde),and CYP1A2 expression were significantly increased(P＜0.01),while GSH content was significantly decreased(P＜0.05),and hepatocyte injury and mitochondrial vacuolation were more serious when compared to control and 1.5 mg/L groups.Conclusions In a mouse model of low-dose ATR liver injury,both 1.5 mg/L and 150 mg/L ATR exposure induced liver injury in mice,with 150 mg/L ATR inducing the maximum metabolic toxicity in the liver after 63 days.

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 investigate the efficacy of CT imaging features in evaluating occult peritoneal metastasis (OPM) of diffuse infiltrating gastric cancer (Borrmann Type Ⅳ).Methods:Totally 101 patients with locally advanced Borrmann type Ⅳ gastric cancer were retrospectively collected who were admitted to Peking University Cancer Hospital from March 2014 to March 2021. The patients were divided into OPM group (53 cases) and the non-OPM group (48 cases) according to the results of preoperative CT and laparoscopic exploration/peritoneal cytology examination. The pathological examination results were recorded, including the degree of histological differentiation and Lauren classification. The evaluation indicators included the tumor center position, the number of tumor-occupied portions, involved orientation, mucosal broadband sign, stratified enhancement, serosa invasion, increased density of peripheral fat tissue, and enlarged lymph nodes. The maximum thickness of the primary tumor, average CT value of the primary tumor (arterial phase, venous phase, and delayed phase), difference between venous phase and arterial phase, difference between delayed phase and venous phase, and pattern of the enhanced curve were recorded. The Mann-Whitney U or Chi-square test was used to compare the differences of pathological and CT features between two groups. The multivariate logistic regression was used to screen independent predictors and establish a nomogram. The receiver operating characteristic curve was used to evaluate the performance of the nomogram in predicting OPM, and the Hosmer-Lemeshow test was used to test the model′s goodness of fit. Results:There was statistical significance in the seven indicators between the OPM and non-OPM groups, including tumor-occupied portions of stomach, mucosal broadband sign, stratified enhancement, serosa invasion, increased density of peripheral fat tissue, the enhanced curve pattern and the degree of histological differentiation ( P<0.05). Among them, the degree of histological differentiation (OR=0.19, P=0.033), stratified enhancement (OR=7.02, P=0.005) and serosa invasion (OR=14.27, P<0.001) were independent predictors of OPM. The nomogram was established based on the three significant features. The area under the curve for predicting OPM was 0.826 (95%CI 0.745-0.908), the sensitivity was 0.566 and the specificity was 0.938. The Hosmer-Lemeshow test showed a good agreement between the OPM risk predicted by the nomogram and the actual risk ( P=0.525). Conclusions:The CT features of Borrmann type Ⅳgastric cancer complicated with OPM have specific characteristics. The diagnosis model based on the degree of histological differentiation, stratified enhancement, and serosa invasion had high efficacy in evaluating OPM.

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.

Objective:To investigate the clinicopathological characteristics, diagnosis, differential diagnosis and prognostic factors of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC).Methods:Sixteen cases of SDSC diagnosed in the Department of Pathology, Beijing Tongren Hospital from January 2016 to September 2020 were enrolled. Ninety-nine cases of small round cell malignant tumors of the head and neck were selected as the control, including poorly-differentiated squamous cell carcinoma ( n=10), poorly-differentiated adenocarcinoma ( n=5), undifferentiated carcinoma (SNUC, n=4), NUT carcinoma ( n=5), neuroendocrine carcinoma ( n=10), and other non-epithelial tumors [olfactory neuroblastoma ( n=10), rhabdomyosarcoma ( n=10), NK/T-cell lymphoma ( n=10), malignant melanoma ( n=10), Ewing′s sarcoma/primitive neuroectodermal tumor (EWS/PNET, n=5)] and non-keratinizing undifferentiated nasopharyngeal carcinoma ( n=20). The clinical and pathologic characteristics of SDSC, and immunohistochemical (IHC) expression of broad-spectrum CKpan, CK7, CK8/18, CK5/6, p63, p40, p16, INI1, NUT and neuroendocrine markers (Syn, CgA, CD56) were evaluated. In situ hybridization (ISH) was used to detect EBER and fluorescence in situ hybridization (FISH) to detect INI1 gene deletion. Results:The 16 cases of SDSC accounted for 1.3% (16/1 218) of all malignant sinonasal tumors in the author′s unit during this time period, and 2.4% (16/657) of all malignant epithelial tumors. Microscopically, there was no clear squamous and adenomatous differentiation, but "rhabdoid-like" cells, are often seen. All SDSC cases were positive for CKpan and CK8/18, negative for INI1; Epstein-Barr virus was not detected by ISH; and INI1 gene deletion was observed in all 11 SDSC patients with FISH. Twelve cases were followed up for 3-47 months. One died of tumor-related diseases half a year after diagnosis, and the remaining patients were alive with tumor, the longest survival time was 47 months.Conclusion:SDSC should be differentiated from a variety of poorly-differentiated tumors in the sinonasal area. Histologically, SDSC has no clear differentiation, but the tumor cells are characteristically basal-like or rhabdoid-like, with non-specific vacuoles, translucent or vacuolar nuclei, prominent nucleoli and necrotic foci. They are negative for INI1 IHC staining, and FISH demonstrates INI1 gene deletion. The clinical prognosis is still unclear, further studies on its biologic behavior and treatment methods are warranted.