Humans ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Mutation/genetics* ; Colorectal Neoplasms/genetics* ; Proto-Oncogene Proteins B-raf/metabolism*

Objective:To investigate the clinical, cytomorphology, immunocytochemical and molecular features of metastatic melanoma in serosal cavity effusion.Methods:Cytological specimens of 14 patients with melanoma in the chest and abdomen were collected from 2017 to 2023, at the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. SOX10, S-100 protein, PRAME, BRAF V600E, HMB45, and Melan A were detected by immunocytochemical methods. Fourteen cases were tested for routine antibody combinations, including Claudin4, HEG1, Calretinin, CD68, etc. Four of the patients had biopsy or surgical samples of metastatic solid lesions of primary sites, and further next-generation sequencing (NGS) or amplification refractory mutation system (ARMS)-PCR molecular test was performed. In addition, 30 cases of serosal effusion samples were collected as control groups (10 cases of benign mesothelial cell reactive hyperplasia, 10 cases of mesothelioma, and 10 cases of metastatic lung adenocarcinoma).Results:Among the 14 cases of melanoma, there were 7 males and 7 females, with ages ranging from 35 to 86 years, and an average age of 57 years, there 10 cases aged ≥50 years. The tumor cells in the serosal effusion varied in morphology and degree of atypia. SOX10 was positive in all 14 cases (14/14), S-100 protein was positive in 10 cases (10/14), PRAME was positive in 12 cases (12/14), BRAF V600E was positive in 10 cases (10/14), HMB45 was positive in 12 cases (12/14), and Melan A was positive in 13 cases (13/14). In 4 patients with histological correlation, the cytological and histological expression of SOX10, BRAF V600E, and PRAME was positive in all 4 cases (4/4); S-100 protein was positive in 2 cases (2/4); and HMB45 and Melan A were positive in 3 cases (3/4). Using NGS or ARMS-PCR, missense mutations of BRAF V600E were detected in all 4 patients; TERT promoter mutations was detected in 1 case; and CDKN2A terminating mutations and MSI1 deletion mutations were detected in the other case. SOX10, S-100, HMB45, Melan A, PRAME and BRAF V600E were all negative in 30 control samples of serosal cavity effusion.Conclusion:By observing the morphology of tumor cells, immunocytochemical test of several combination markers, especially the expression of SOX10, BRAF V600E and PRAME, can help to improve the positive diagnosis rate of melanoma in serous cavity effusion.

Stevens-Johnson syndrome (SJS), also known as the multifactorial erythematous drug eruption, is a class of adverse reactions of the skin and mucous membranes primarily caused by drug allergy often involving the oral cavity, eyes, and external genital mucosa, generally accompanied by fever, and can be life-threatening in severe cases. In February 2022, the Department of Stomatology, the First Affiliated Hospital of Zhengzhou University admitted a patient with huge inflammatory hyperplasia of bilateral lingual margins secondary to SJS. Upon admission, no other obvious symptoms were observed except for tongue hyperplasia. The patient suffered from a severe adverse drug reaction caused by acetaminophen 2 months ago and was complicated by liver dysfunction and pulmonary infection. After 1 month of treatment and rehabilitation, he developed a secondary tongue mass and was subsequently admitted to Dept. of Oral and Maxillofacial Surgery Ward 2, the First Affiliated Hospital of Zhengzhou University. After completing the examination, the tongue mass was surgically removed. After a follow-up of 11 months, the patient's condition was satisfactory and no temporary discomfort was observed. The case of tongue mass secondary to SJS is extremely rare. If a stomatologist encounters a similar case, we should carefully inquire about the drug allergy history and recent medication history, and be alert to whether or not they had adverse drug reactions recently.
Male ; Humans ; Stevens-Johnson Syndrome/drug therapy* ; Hyperplasia/pathology* ; Skin ; Drug Hypersensitivity/pathology* ; Tongue

Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide, but the molecular basis underlying its development remains unclear. An accumulating body of evidence supports gasdermin D (GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases. However, there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis. In this work, we investigated the role of GSDMD-mediated pyroptosis in silicosis. Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression. Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica. Measurement of interleukin-1β release, lactic dehydrogenase activity, and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages. Additionally, we verified that both canonical (caspase-1-mediated) and non-canonical (caspase-4/5/11-mediated) signaling pathways mediated silica-induced pyroptosis activation, in vivo and in vitro. Notably, Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes, which highlighted the pivotal role of pyroptosis in this disease. Taken together, our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.

Objective:To explore the clinical, pathological and genetic characteristics of early-onset facioscapulohumeral muscular dystrophy type 1 (FSHD1), in order to increase awareness of the disease.Methods:In this retrospective study, the history of 3 patients, who were diagnosed with early-onset FSHD1 by molecular genetic test in Pediatric Outpatient Department of Peking University First Hospital from 4 th June 2012 to 4 th June 2018, were collected. Their clinical data, genotypes, phenotypes and pathological features of muscle biopsy were analyzed. Results:All the three patients were males at the age of 14 years, 11 years and 9 years 11 months, respectively, whose onset age was between infancy and early childhood and they got confirmed diagnosis within 4 to 10 years after the onset of illness. Their molecular genetic testing indicated that the number of D4Z4 repeat arrays located in 4qA were 2, 3 and 4, which was consistent with the characteristics of early-onset FSHD1. Their common clinical manifestations were facial, scapular and proximal lower limb muscle progressively and asymmetrically weakness. All patients had different severity of spine deformity and high-frequency dominant sensorineural hearing loss, however, the phenotype of the third patient with 4 D4Z4 repeats was significantly the most severe.Conclusions:Early-onset FSHD1 usually concealed onset and is difficult to diagnose. Its precise diagnosis depends on molecular genetic techniques, but the genotypes of 3 patients here are not corresponding to phenotypes strictly and it is necessary to accumulate more cases for further analysis in order to provide a more reliable basis for the relationship of genotype-phenotype and prognosis evaluation of the disease.

Objective To compare the clinical effects of G-arm X-ray machine and C-arm X-ray machine in percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF) of thoracolumbar spine.Methods The clinical data of ninety-five patients with thoracolumbar OVCF treated with PKP from May 2016 to August 2017 in Yanan University Affiliated Hospital were retrospectively analyzed.They were divided into two groups according to the different guiding fluoroscopy methods used during the operation.Forty-six cases in G arm group completed PKP under the guidance of G arm X-ray machine,Forty-nine cases in C arm group completed PKP under the guidance of C arm X-ray machine.The operation time,fluoroscopy times,cement leakage cases,the height of injured vertebral leading edge,Cobb angle of kyphosis,visual analogue score and Oswestry dysfunction index were recorded before and after operation,and the related indexes were analyzed and compared.Results Two groups of patients were successfully completed surgery,no complications of vascular and nerve injury.The operation time and fluoroscopy times in G arm group were less than those in C arm group (operation time:(29.6±4.5) min vs.(42.5±5.3) min,and fluoroscopy times in G arm group:(9.1±2.0) vs.(16.9±3.2));the difference was statistically significant (t =-12.747,12.870,P＜ 0.01).Postoperative height of injured vertebral leading edge(G arm group (22.3±5.3) mm),C arm group (22.4±5.1) mm),kyphosis Cobb angle (G arm group (9.2±3.8)°,C arm group (9.3±3.7) o),visual analogue score (G arm group (2.1±0.7)points,C arm group (2.2±0.9) points),Oswestry dysfunction index (G arm group (21.3±8.5) points,C arm group(21.5 ± 8.3)points),compared with preoperative(the hight of injured vertebral leading edge of G arm group (18.2 ±5.3) mm,C arm group (18.4±5.2) mm,Cobb angle of injured vertebra G arm group (15.7±4.4) °,C arm group (15.9±4.3) °,visual analogue score of G arm group (7.8± 1.2) points,C arm group (7.7± 1.1) points,Oswestry dysfunction index score of G arm group(41.2±8.3)points,C arm group (41.5±8.2) points),the difference was statistically significant (t =-3.709,-3.844,-7.582,-8.144,27.827,27.088,11.360,11.999,P＜0.01),but there was no significant difference between the two groups (P ＞0.05).Conclusion Using G-arm X-ray machine to assist PKP in the treatment of thoracolumbar spine OVCF can effectively shorten the operation time,reduce the intraoperative fluoroscopy time,and the clinical effect is satisfactory.

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.

Four new limonoid-type nortriterpenoids, 1-detigloyl-1--methacryloylsalannin (), 28-deoxo-2,3-dihydronimbolide (), 12-acetoxy-3--acetyl-7--tigloylvilasinin () and 12-acetoxy-3--acetyl-7--methacryloylvilasinin (), along with five known ones, were isolated from seeds of A. Juss. Their structures were elucidated by various spectroscopic methods, including UV, IR, MS, NMR, X-ray crystallography, quantum chemical calculation, as well as by comparison of their spectroscopic data with those reported. In the cytotoxic assay, showed inhibitory activity against human breast cancer MDA-MB-231 cell line with IC value of 7.68±1.74 μmol/L, and inhibited growth of human cervical cancer Hela cell line, melanoma A375 cell line and promyelocytic leukemia HL-60 cell line, with IC 12.00±2.08, 17.44±2.11, and 13.95±5.74 μmol/L, respectively.

Objective To investigate the relationship between single nucleotide polymorphism(SNP)of the peroxisome proliferator activated receptor γ (PPARγ) gene Rs1801282 and brick-tea type fluorosis. Methods From 2012 to 2013, this cross-sectional study was performed in 16 endemic fluorosis areas of brick-tea type in Inner Mongolia Autonomous Region,Qinghai and Xinjiang Uygur Autonomous Region of China,to select adults>18 years old as subjects, who were diagnosed as skeletal fluorosis by X-ray. All of the subjects filled in demography survey questionnaire; the survey contents included general characteristic s, and average daily brick tea intake. Drinking tea samples and urine samples of each subject were collected, and fluoride content of urine and brick-tea was determined via the ion selective electrode method (WS/T 89-2006). X-ray scintigraphy was used to diagnose skeletal fluorosis, according to the "Diagnostic Criteria of Endemic Skeletal Fluorosis" (WS/T 192-2007); the subjects were divided into skeletal fluorosis group (case group) and non-skeletal fluorosis group (control group). To collect venous blood 5 ml, whole blood DNA was extracted, and polymorphism at Rs1801282 of PPARγ was detected by MassARRAY time-of-flight mass spectrometry, to calculate odds ratio (OR) and 95% confidence interval (CI). Results There were 1 414 people included in this study,including 347 in case group and 1 067 in control group. By the Hardy-Weinberg balance test, the PPARγ gene Rs1801282 genotype was representative in case group, control group and each nationality (P > 0.05). The difference of PPARγ gene Rs1801282 genotype in case group and control group was not statistically significant (OR was 0.991, 95%CI: 0.704 - 1.395, the adjusted OR was 1.026, 95%CI: 0.707-1.489).The difference of PPARγ gene Rs1801282 genotype(CC,CG+GG)in case group and control group in different nationality was not statistically significant (Tibetan: OR was 1.400, 95%CI: 0.576 - 3.404, the adjusted OR was 1.258, 95%CI: 0.474 - 3.340; Kazak: OR was 0.898, 95%CI:0.516 -1.562,the adjusted OR was 0.936,95%CI:0.532 -1.648;Mongolia: OR was 1.148,95%CI:0.508-2.594, the adjusted OR was 1.644, 95%CI: 0.683 - 3.956; Han: OR was 1.058, 95%CI: 0.451 - 2.482, the adjusted OR was 0.959, 95%CI: 0.388 - 2.371; Russian: OR was 0.000, 95%CI: 0.000 - 0.000, the adjusted OR was 0.000, 95% CI: 0.000 - 0.000) with binary Logistic regression analysis. Conclusion We have found no association between SNP of PPARγ gene Rs1801282 and skeletal fluorosis of brick-tea type fluorosis in China.

Objective: The purpose is to investigate the validity of a surgical technique that utilizes autologous costal cartilage grafts in primary rhinoplasty for female patients. Methods: From July 2015 to July 2017, 137 cases received primary rhinoplasty with various types of grafts originated from autologous costal cartilage to correct the unpleasant nasal appearances including low dorsum, poorly defined nasal tip and wide alar base. Results: With 6 to 36 months follow-up, six patients(4.3%) exhibited noticeable changes in nasal contour due to graft warping. Revision surgeries were commenced to correct those minor deformities, resulting in satisfactory outcome.All other cases presented significant improvements of the nasal appearance. Conclusions Autologous costal cartilage is a good source for primary rhinoplasty cases.