Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Objective To investigate the identification of octreotide(OCT)modified chitosan(CS)miR-155 molecular beacon nanoparticles(CS-miR-155-MB-OCT)and imaging of lung cancer cells for the early screening of lung cancer.Methods A nude mouse model of lung transplantation tumor was established by injecting A549 lung cancer cells into tail veins to establish lung xenograft models.Cre adenovirus was injected through nasal cavity,and mice were killed at 4,6,8 and 12 weeks after adenovirus injection to establish lung cancer models of atypical hyperplasia,adenoma,carcinoma in situ and adenocarcinoma of lung in LSL K-ras G12D transgenic mice at different pathological stages.Lung tissue samples were taken and observed by HE staining.Immunohistochemistry were used to detect the expression of somatostatin receptor 2(SSTR2).Real-time fluorescence quantitative PCR was used to detect miR-155 expression levels in lung xenograft models and transgenic mice at different stages of lung cancer.Then CS-miR-155-MB and CS-miR-155-MB-OCT were injected via tail vein in lung xenograft models.CS-miR-155-MB-OCT was injected via tail vein in transgenic mice models.The fluorescence signals of lung in nude mice and transgenic mice at different disease stages were imaged by living imaging system.Frozen slices of lung tissue were made.The source of fluorescence signal was detected by laser confocal scanning microscope(CLSM).Results HE staining showed that lung transplantation tumor models and lung cancer models of atypical hyperplasia,adenoma,carcinoma in situ and lung adenocarcinoma at different pathological stages were successfully constructed.Immunohistochemical analysis showed somatostatin receptor 2(SSTR2)was expressed in transplanted lung tumor and tissue at different pathological stages.In transgenic mouse models,the expression of miR-155 was gradually increased as the disease progressed(P＜0.05).In lung xenograft models,the fluorescence signals were significantly higher in the CS-miR-155-MB-OCT group than those of the CS-miR-155-MB group(P＜0.05).In transgenic mouse models,the fluorescence signals gradually increased with the gradual progression of lesions(P＜0.05).After re-imaging the lung tissue,it was found that the fluorescence signal came from lung,and CLSM showed that the fluorescence signal came from cancer cells and some normal alveolar epithelial cells.Conclusion CS-miR-155-MB-OCT can dynamically reflect the occurrence and development of lung cancer according to changes of different fluorescence intensity,thus providing a new technology for the early diagnosis of lung cancer.

Objective:To explore the correlation between MYB/NFIB gene fusion and clinicopathological features such as tumor grade and prognosis of head and neck adenoid cystic carcinoma (ACC), and to assess the concordant rate of fluorescent in situ hybridization (FISH) with MYB and NFIB immunohistochemistry.Methods:FISH detection of MYB/NFIB gene fusion was performed on 48 head and neck ACC cases and 15 non-ACC salivary gland tumors at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China during April 2014 and January 2020. ACC cases were divided into grade Ⅰ-Ⅱ, grade Ⅲ and high-grade transformation, according to pathological grading criteria. Prognosis, FISH results and other clinicopathological characteristics were analyzed. MYB and NFIB immunohistochemistry was performed on the 48 ACC and 15 non-ACC cases. The diagnostic accuracy of FISH and immunohistochemistry was compared.Results:FISH detected MYB/NFIB gene fusion in 41.7% (20/48) of the ACC. Its positive rate was inversely correlated with higher pathological grades ( P=0.036). The higher histological grade was linked to worse progression-free survival ( P=0.024), whereas there was no correlation between the status of gene fusion detected by FISH and progression-free survival ( P=0.536). FISH didnot detect MYB/NFIB gene fusion in 15 non-ACC salivary gland tumors The specificity of diagnosing ACC is 100% for both FISH detection of gene fusion and immunohistochemical detection of MYB expression. However, the sensitivity for both methods was only about 41.7%, respectively. By combining FISH and MYB immunohistochemistry, the sensitivity for diagnosing ACC was increased to 66.7%. Conclusions:MYB/NFIB gene fusion has a lower detection rate in grade Ⅲ ACC and high-grade transformation ACC. Meanwhile gene fusion status is not correlated with prognosis. The sensitivity for diagnosing ACC can be improved by combining FISH and MYB immunohistochemistry.

Objective:To explore the expressions of long non-coding RNA LINC00673 and ISG15 protein in pancreatic cancer and their clinical significances.Methods:The clinical data of 57 patients diagnosed as pancreatic ductal carcinoma (PDAC) at the Affiliated Cancer Hospital of Xiangya Medical College of Central South University from January 2014 to December 2018 were retrospectively analyzed. The relative expressions of LINC00673 in pancreatic cancer tissues and paracancerous normal tissues (within 3 cm from the edge of cancer tissues) were examined by using quantificational reverse transcription-polymerase chain reaction (qRT-PCR). The ISG15 protein expressions in pancreatic cancer tissues and paracancerous normal tissues were examined by using immunohistochemistry. The difference in LINC00673 expression between ISG15 protein positive and negative patients was compared. The correlation between LINC00673 and ISG15 protein expressions in pancreatic cancer was analyzed by Spearman rank correlation analysis. Moreover, the correlations of LINC00673 and ISG15 protein expressions with clinical stage and pathological classification of pancreatic cancer patients were analyzed.Results:The positive expression of ISG15 protein in pancreatic cancer tissues was 40.4% (23/57), which was higher than that in paracancerous normal tissues [15.8% (9/57)] ( χ2 = 7.90, P = 0.004), and the relative expression of LINC00673 in pancreatic cancer tissues was 0.99±0.36, which was lower than that in paracancerous normal tissues (1.26±0.41) ( t = 4.80, P < 0.001). For 23 (40.4%) ISG15-positive patients and 34 (59.7%) ISG15-negative patients, the relative expression of LINC00673 was 0.77±0.46 and 0.45±0.27 ( P < 0.001). Spearman analysis showed that there was a correlation between LINC00673 and ISG15 protein expressions ( ρ = -0.429, P = 0.001). The relative expression of LINC00673 decreased in patients with low differentiated or undifferentiated tumor, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between LINC00673 expression and patients' age, tumor site, preoperative CA199 level, and TNM stage (all P > 0.05); ISG15 protein expression increased in patients with low differentiated or undifferentiated tumor, TNM stage Ⅲ-Ⅳ, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between ISG15 protein expression and patients' gender, age, tumor site, and preoperative CA199 level (all P > 0.05). Conclusions:The expression of LINC00673 in pancreatic cancer is related to vascular invasion, tumor differentiation degree and lymph node metastasis, and the expression of ISG15 in pancreatic cancer is related to vascular invasion, tumor differentiation degree, lymph node metastasis and TNM stage. The combined detection of LINC00673 and ISG15 protein could be a valuable prognostic indicator for pancreatic cancer. The therapies targeting LINC00673 and ISG15 protein signaling pathways are expected to be a potential option for immunotherapy of pancreatic cancer.

Objective:To study the clinical characteristics and prognosis of Brucella and other pathogens infections complicated with anti-myelin oligodendrocyte glycoprotein-IgG associated disorders (MOGAD). Methods:The clinical data of a patient with brucellosis complicated with MOGAD diagnosed in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University in April 2022 were reported, and related case reports of infection coexisting with MOGAD were reviewed and summarized.Results:This case was a 44-year-old male, with recurrent fever and anorexia, followed by sudden weakness, numbness, pain in both lower limbs and dysuria, and then pain in the right neck. Magnetic resonance imaging showed lesions in the spine and spinal cord. Due to the positive myelin oligodendrocyte glycoprotein antibodies in cerebrospinal fluid and serum, and the growth of Brucella in blood culture, he was diagnosed as brucellosis complicated with MOGAD. After anti-brucellosis and glucocorticoid therapy, his symptoms improved. The literature on infection coexisting with MOGAD was reviewed and 22 cases were included. The infection sources included COVID-19, Borrelia burgdorferi, etc. No case of Brucella infection complicated with MOGAD had been reported. The main clinical manifestations of the 22 cases included myelitis (63.6%, 14/22), optic neuritis (40.9%, 9/22), acute disseminated encephalomyelitis (18.2%, 4/22), multiphasic disseminated encephalomyelitis (4.5%, 1/22) and meningoencephalitis (4.5%, 1/22). Magnetic resonance imaging was performed in 20 cases, showing spinal cord lesions in 12 cases (60.0%, 12/20), intracranial lesions in 10 cases (50.0%, 10/20) and optic nerve lesions in 6 cases (30.0%, 6/20). Cerebrospinal fluid examination was performed in 19 patients, of whom 13 (13/19) had increased cerebrospinal fluid cell count and 10 (10/18) had increased cerebrospinal fluid protein. Twenty-two patients received glucocorticoid therapy, of which 95.5% (21/22) responded well and 95.5% (21/22) had a good prognosis. Conclusions:Brucella and other pathogens infection may complicate with MOGAD, with similar clinical manifestations, and glucocorticoid therapy is effective.

Objective:To analyze the survival of 451 hospitalized patients with gallbladder cancer from Nantong Tumor Hospital,and provide evidence for prognosis evaluation and comprehensive prevention and treatment of gallbladder cancer. Methods:A combination of active and passive follow-up methods were used to trace the survival outcomes of patients with gallbladder cancer hospitalized in Nantong Tumor Hospital from 2007 to 2017.The gender and age distribution,as well as the trend in the change of the number of patients over time was statistically analyzed.Kaplan-Meier method was used to analyze the survival rate of the patients,and Log-rank test was used to compare the difference in the survival rate of patients with different gender,age,TNM staging and time period of hospitalization. Results:A total of 451 hospitalized patients with gallbladder cancer from 6 counties/districts in Nantong area from 2007 to 201 7 were included in this study.Cancer survival outcomes of 449 patients were obtained through follow-up,with a success rate of 99.56％.Among them,218 were male and 233 were female,and the average age at the initial hospitalization was(64.78±11.44)years,with a median age of 67 years.The majority of the patients were aged 60-79 years old,accounting for 60.75％(274 cases)of the patients.The 1-,3-,and 5-year observed survival rates of all patients were 34.59％,15.30％,and 10.25％,respectively.The 5-year survival rates of male and female patients were 7.75％and 12.47％respectively,with no statistically significant difference between the two groups(P＞0.05).The 5-year survival rates of patients in the age groups of 0-34 years,35-59 years,60-79 years,and ≥80 years were 25.00％,14.53％,8.66％,and 2.94％,respectively,with statistically significant differences(P＜0.01).The 5-year survival rates stratified by TNM stage were 27.78％,20.83％,13.44％,3.48％and 11.11％,for stage Ⅰ,Ⅱ,Ⅲ,Ⅳ,and unclassified,respectively,with statistically significant differences(P＜0.001).The 5-year survival rates of patients with gallbladder cancer hospitalized from 2007 to 2011 and from 2012 to 2017 were 10.81％and 9.99％,respectively,with no statistically significant difference(P＞0.05). Conclusion:Patients with gallbladder cancer in Nantong from 2007 to 2017 were mainly middle-aged people and elderlies,and the survival rates of these patients significantly decreased with increasing age,with no significant difference observed in different gender groups,indicating the need to strengthen the research for comprehensive prevention and treatment for middle-aged and elderly patients to improve their prognosis.

Background::The differential diagnosis of mucoepidermoid carcinoma (MEC) from neoplasm undergoing mucinous features brings more pitfalls to pathologists. Combining specific MAML2 gene rearrangement and histological characteristics may be the solution. Methods::Twenty-five tumors with mucinous components were selected for differential diagnosis of MEC. All the cases were detected for MAML2 gene rearrangement. The cases diagnosed as MEC were classified into four variants: classic, oncocytic, Warthin-like, and nonclassified, and they were graded using the Brandwein system. The histological characteristics of non-MECs were summarized for differential diagnosis. Univariate survival analysis was performed on MECs. Results::There were 16 MECs; 62.5% were MAML2 rearranged. For the low-, intermediate-, and high-grade MECs, the rate of rearrangement was 83.3%, 100%, and 28.6%, respectively. Both the oncocytic and Warthin-like MECs were MAML2 rearranged. For the classic and nonclassified MECs without MAML2 rearrangement, non-keratinized squamoid cells and distinctive mucinous cells were essential diagnostic criteria. On survival analysis, all the disease progression occurred in high-grade MECs ( p = 0.038). Nine cases were diagnosed as non-MECs: pleomorphic adenoma with mucinous metaplasia showed no ex-capsular involvement; metaplastic Warthin tumor appeared with overt keratinization and residual oncocytic bilayered epithelium; mix squamous cell and glandular papilloma showed an endobronchial papillary growing pattern; adenosquamous carcinoma was accompanied by squamous carcinoma in situ of the overlying mucosa. All the non-MECs were negative for MAML2 rearrangement. Conclusion::The application of combining MAML2 rearrangement and histological characteristics is helpful in the differential diagnosis between MEC and other tumors with mucinous components.

Background::The differential diagnosis of mucoepidermoid carcinoma (MEC) from neoplasm undergoing mucinous features brings more pitfalls to pathologists. Combining specific MAML2 gene rearrangement and histological characteristics may be the solution. Methods::Twenty-five tumors with mucinous components were selected for differential diagnosis of MEC. All the cases were detected for MAML2 gene rearrangement. The cases diagnosed as MEC were classified into four variants: classic, oncocytic, Warthin-like, and nonclassified, and they were graded using the Brandwein system. The histological characteristics of non-MECs were summarized for differential diagnosis. Univariate survival analysis was performed on MECs. Results::There were 16 MECs; 62.5% were MAML2 rearranged. For the low-, intermediate-, and high-grade MECs, the rate of rearrangement was 83.3%, 100%, and 28.6%, respectively. Both the oncocytic and Warthin-like MECs were MAML2 rearranged. For the classic and nonclassified MECs without MAML2 rearrangement, non-keratinized squamoid cells and distinctive mucinous cells were essential diagnostic criteria. On survival analysis, all the disease progression occurred in high-grade MECs ( p = 0.038). Nine cases were diagnosed as non-MECs: pleomorphic adenoma with mucinous metaplasia showed no ex-capsular involvement; metaplastic Warthin tumor appeared with overt keratinization and residual oncocytic bilayered epithelium; mix squamous cell and glandular papilloma showed an endobronchial papillary growing pattern; adenosquamous carcinoma was accompanied by squamous carcinoma in situ of the overlying mucosa. All the non-MECs were negative for MAML2 rearrangement. Conclusion::The application of combining MAML2 rearrangement and histological characteristics is helpful in the differential diagnosis between MEC and other tumors with mucinous components.

Objective:To analyze the survival rate of malignant tumor in the elderly over 60 years old in Qidong city from 1972 to 2016, and to provide basis for prognosis evaluation and prevention.Methods:Based on the data of 66 386 patients with malignant tumor in the elderly over 60 years old in the Qidong cancer registration and reporting system, the survival outcome was tracked by the method of active follow-up and passive follow-up.All of these data were then analyzed by stratification of sex, age, tumor site and hospital level.Results:During the period of 1972 to 2016, the total number of patients with malignant tumors in the elderly were 66 386 cases, accounting for 56.66% of patients in all age groups.The observed survival rate(OSR)of 5 and 10 years were 14.52% and 9.53% and relative survival rate(RSR)of 5 and 10 years were 19.76% and 18.92%, respectively, in the elderly in Qidong.The 5-year RSR was 16.98% for males and 23.91% for females, being a statistically significant( χ2=339.83, P<0.001). The 5-year RSRs of elderly patients in males and females increased from 7.53% and 15.83% in 1972-1976 to 28.06% and 39.01% in 2012-2016, respectively.The 5-year RSR of 60-64, 65-69, 70-74, 75-79, 80-84 and 85 years old and over were 22.84%, 20.53%, 17.74%, 18.30%, 18.02% and 14.06%, respectively, with a statistically significant difference( χ2=694.27, P<0.001). Among the top 10 major malignancies, the ranks of 5-year RSR from high to low were breast cancer, prostate cancer, bladder cancer, colorectal cancer, malignant lymphoma, gastric cancer, liver cancer, esophageal cancer, lung cancer, and pancreatic cancer, respectively.A comparison between 2002--2016 and 1972--1986 showed that the increased rank of absolute values of RSR from highest to lowest were prostate cancer, colorectal cancer, female breast cancer, bladder cancer, gastric cancer, malignant lymphoma, liver cancer, esophageal cancer, lung cancer, and pancreatic cancer, respectively.The 5-year RSR of patients diagnosed in the district / township hospitals, county hospitals, city-level 3A hospitals and provincial-level 3A hospitals were 13.97%, 23.71%, 26.12% and 28.55%, respectively, with a statistically significant difference( χ2=841.93, P<0.001). In the 45 years, the average annual percentage change(AAPC)ratio of 5-year OSR was 3.88%( t=6.75, P<0.001), and the 5-year RSR was 3.69%( t=7.44, P=0.001); the AAPC of the 5-year RSR was 3.91%( t=9.66, P<0.001)in males and 3.42%( t=6.08, P=0.001)in females.The AAPC ratio of 5-year RSR in each age group were 4.08% for 60-64 years, 4.18% for 65-69 years, 3.91% for 70-74 years, 3.12% for 75-79 years, 3.81% for 80-84 years, 0.51% for 85 years old and over, respectively.Except for age group of 85 years old and over( P=0.615), significant rising trends were observed in all age groups( P<0.01). Conclusions:Malignant tumors in the elderly have become the major cancer burden in Qidong, and there are significant gender and age differences.The overall survival rate in elderly patients with malignant tumors has been significantly improved in the past 45 years, which may be related to the improvement in the level of diagnosis and treatment and the service capacity of hospitals.

Objective To investigate the predictive value of depth of invasion (DOI) of tongue squamous cell carcinoma (TSCC) for cervical lymph node metastasis and prognosis. Methods We retrospectively analyzed the clinical and pathological data of 73 patients with T_1/2 TSCC. ROC curve was used to determine the optimal cut-off value of DOI for predicting cervical lymph node metastasis, and logistic regression analysis was performed to analyze the related factors affecting cervical lymph node metastasis of TSCC. Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results Among 73 patients, 18 patients were with lymph node metastasis and 55 patients were without lymph node metastasis. The median DOI with and without lymph node metastasis were 8.00 and 5.00 mm, respectively (P=0.003). The optimal cut-off value for DOI was 6.15 mm, with AUC 0.75 (95%CI: 64.1%~87.1%, P=0.001), sensitivity 77.8% and specificity 63.6%. DOI and pathological differentiation were independent prognostic factors for cervical lymph node metastasis in multivariate analysis. DOI, nerve invasion and pathological differentiation were independent prognostic factors of survival in Cox regression analysis. Conclusion DOI of TSCC patients has important predictive value for both cervical lymph node metastasis and prognosis. Neck lymph node dissection is recommended for patients with DOI > 6.15 mm to improve survival rate and reduce recurrence rate.