MRI radiomics for predicting intracranial progression in non-small-cell lung cancer patients with brain metastases treated with epidermal growth factor receptor tyrosine kinase inhibitors.

AIM: To identify clinical and magnetic resonance imaging (MRI) radiomics predictors specialised for intracranial progression (IP) after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in non-small-cell lung cancer (NSCLC) patients with brain metastases (BMs). MATERIALS AND METHODS: Seventy EGFR-mutated NSCLC patients with a total of 212 BMs who received first-line EGFR-TKI therapy were enrolled. Radiomics features were extracted from the BM regions on the pretreatment contrast-enhanced T1-weighted images, and the radiomics score (rad-score) of each BM was established based on the selected features. Furthermore, the mean rad-score derived from the average rad-score of all included BMs in each patient was calculated. Univariate and multivariate logistic regression analyses were performed to identify potential predictors of IP. Prediction models based on different predictors and their combinations were constructed, and nomogram based on the optimal prediction model was evaluated. RESULTS: Thirty-three (47.1 %) patients developed IP, and the remaining 37 (52.9 %) patients were IP-free. EGFR-19del mutation (OR 0.19, 95 % CI 0.05-0.69), third-generation TKI treatment (OR 0.33, 95 % CI 0.16-0.67) and mean rad-score (OR 5.71, 95 % CI 1.65-19.68) were found to be independent predictive factors. Models based on these three predictors alone and in combination (combined model) achieved AUCs of 0.64, 0.64, 0.74, and 0.86 and 0.64, 0.64, 0.75, and 0.84 in the training and validation sets, respectively, and the combined model demonstrated optimal performance for predicting IP. CONCLUSIONS: The model integrating EGFR-19del mutation, third-generation TKI treatment and mean rad-score had good predictive value for IP after EGFR-TKI treatment in NSCLC patients with BM.

[Clinical, imaging and pathological and molecular characteristics of simple bone cyst].

Objective: To investigate the radiologic, pathologic, and molecular features of simple bone cysts (SBC), and their differential diagnoses. Methods: Fourteen cases of SBC were collected at the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from 2017 to 2022, and fluorescence in situ hybridization (FISH) was performed for retrospective analysis. Results: There were 14 patients, including 7 females and 7 males, with age range of 7 to 45 (median 29) years. The most common complaint was pain, including 4 cases with pathological fracture and 5 with history of previous trauma. The tumor size ranged from 3.4 to 13.5 (median 5.6) cm. The lesion involved the femur (n=4), humerus (n=5) and iliac bone (n=5). Radiologic diagnoses included SBC, aneurysmal bone cyst, and giant cell tumor of the bone or its combination with aneurysmal bone cyst-like region and fibrous dysplasia. Histologically, the cyst walls of the lesions were composed of fibrous tissue, fibrin-like collagen deposits, bone-like matrix and occasional woven bone. The lesional cells were spindled to ovoid, with scattered osteoclast-like giant cells, foamy histiocytes, hemosiderin deposits and cholesterol clefts. In 6 cases there were nodular fasciitis-like areas. Immunohistochemically, the spindled to ovoid cells were positive for SMA, EMA and SATB2 in varying degrees. FISH detection was performed in all 14 cases and EWSR1/FUS rearrangement were found in 9 cases. One case of FUS::NFATC2 fusion was detected by next-generation sequencing. Nine cases of SBC with the rearrangement were more cellular, and there were more mitotic figures in the recurrent FUS::NFATC2 fusion tumor. Clinical follow-up was obtained in all 14 cases with the time ranging from 5 to 105 (mean 46) months. Amongst them, the tumor with FUS::NFATC2 rearrangement had local recurrence twice after the first local excision, but had no more recurrence or metastasis 34 months after the subsequent segmental resection. The other 13 cases had no recurrence. Conclusions: EWSR1 or FUS rearrangement is most commonly identified in SBC, suggesting that SBC might be a neoplastic disease. In cases where the radiologic appearance and histomorphology are difficult to differentiate from aneurysmal bone cyst, FISH detection can aid in the definitive diagnosis.

Modifiable predictors of type 2 diabetes mellitus and roles of insulin resistance and ß-cell function over a 6-year study and 30-year follow-up.

PURPOSE: This study aimed to examine the modifiable predictors of T2DM and the roles of insulin resistance (IR) and ß-cell function over a 6-year study and 30-year follow-up. METHODS: A total of 462 non-diabetic participants, 282 with impaired glucose tolerance (IGT), and 180 with normal glucose tolerance (NGT) were enrolled in this analysis. The Matsuda IR index and area under the curve of insulin-to-glucose ratio (AUCI/G-R) were used as IR and ß-cell function indices in the analysis. RESULTS: In all participants, multivariable analysis showed that BMI, glucose status, Matsuda IR index and systolic blood pressure (SBP) at baseline were independently associated with an increased risk of T2DM over 30 years, whereas lifestyle intervention and AUCI/G-R were inversely associated with this risk. The predictive effect of the Matsuda IR index and AUCI/G-R in participants with IGT was consistent with the results of all participants, whereas in those with NGT, only the Matsuda IR index, not the AUCI/G-R, predicted the development of T2DM (HR = 1.42, 95% CI 1.07-1.89 vs HR = 1.09, 95% CI 0.76-1.56). The predictive effect of the Matsuda IR index on T2DM existed even in participants with BMI < 25 (p = 0.049). CONCLUSION: The modifiable predictors of T2DM in Chinese adults were high BMI, hypertension, mild hyperglycaemia, IR, and ß-cell dysfunction. Both IR and ß-cell function contributed to the development of T2DM in the long term; however, IR remains the initial and long-standing key risk factor for T2DM.

[Expression of glycolytic genes in immune cells and changes of related immune cells in experimental autoimmune neuritis].

Objective: To investigate the expression of glycolytic genes in immune cells and the changes of related immune cells in experimental autoimmune neuritis (EAN), and deepen the understanding of pathogenesis of EAN. Methods: Twenty-four male C57BL/6 mice (6-8 weeks old, 18-20 g) were divided into four groups according to the random number table method: control group (P0180-199 was replaced by PBS during modeling and mice were sacrificed on the 16th day), EAN mice were sacrificed on the 8th day after the end of modeling (EAN 8 d), EAN mice were sacrificed on the 16th day after the end of modeling (EAN 16 d), and EAN mice received drug intervention and were sacrificed on the 16th day after the end of modeling (2-DG was intraperitoneally injected since the day of the first immunization, 550 mg/kg; EAN 16 d+2-DG), with 6 rats in each group. The clinical symptoms and clinical scores were observed and recorded daily. At the end of the experiment, the mice were sacrificed under chloral hydrate anesthesia, and the serum, spleen, sciatic nerve and other tissues of each group were collected. The degree of inflammatory cell infiltration and demyelination of sciatic nerve were observed by hematoxylin and eosin (HE) staining and luxol fast blue (LFB) staining. Flow cytometry was used to detect the proportion of M1 macrophages, Th17 cells and Tregs cells. The mRNA expression levels of glycolysis-related genes (mTORC1, HIF1α, GLUT1 and LDHA) were detected by RT-PCR. Western blotting was used to detect the level of pan-lysine lactate in macrophages and sciatic nerve tissue. Results: The expression of glycolysis-related genes (mTORC1, HIF1α, GLUT1 and LDHA) in spleen M1 macrophages and sciatic nerve was significantly up-regulated in EAN 16 d group, compared with control, EAN 8 d and EAN 16 d+2-DG groups (all P<0.05). The relative pan-lysine lactate (pankla) expression level of spleen M1 macrophages (1.25±0.02) and sciatic nerve tissue (1.23±0.26) significantly increased in EAN 16 d group, compared with control, EAN 8 d and EAN 16 d+2-DG groups (M1 macrophages: 0.12±0.10, 1.07±0.12 and 0.42±0.07; sciatic nerve: 0.10±0.12, 0.87±0.20 and 0.36±0.05) (all P<0.05). The expression of glycolytic genes in splenic CD4+T cells showed an increasing trend, but there were no statistically significant differences among the groups, and the expression of glycolytic genes did not decrease significantly after 2-DG treatment (all P>0.05). The proportion of spleen M1 macrophages in the control group, EAN 8 d group, EAN 16 d group and EAN 16 d+2-DG group was 4.28±0.13, 7.54±0.25, 13.16±0.33 and 4.13±0.38 respectively, which was significantly higher in the EAN 16 d group (all P<0.05). The proportion of spleen Th17 cells in the four groups was 3.78±0.03, 8.24±0.55, 12.30±1.34 and 4.83±0.01, respectively, which was significantly higher in the EAN 16 d group (all P<0.05). The proportion of spleen Tregs cells in the four groups was 10.01±1.05, 7.54±0.70, 3.82±0.47 and 8.22±1.21, respectively, which was significantly lower in the EAN 16 d group (all P<0.05). Conclusions: The expression of glycolytic genes in splenic macrophages significantly increases during EAN, but not in CD4+T cells. The proportion of M1 macrophages and Th17 cells in spleen gradually increases, while the proportion of Tregs cells gradually decreases.

[Incidence and risk factors of acute mountain sickness in grid construction personnel working at plateau].

Objective: To analyze the incidence and risk factors of acute mountain sickness (AMS) in grid construction personnel working at plateau. Methods: A total of 10 956 plateau construction personnel of Ali Network Project from January 1, 2019 to December 31, 2020 were included. Baseline information (including age, sex, body mass index, developmental and nutritional status, relevant clinical indicators, etc.) and follow-up data of AMS were obtained from the medical record of Ali Internet engineering staff medical station. The altitude of the residence place in early life and the working environment were obtained from the website (https://zh-cn.topographic-map.com/legal/). The incidences of overall AMS and its subgroups were calculated, and the Cox proportional hazards model was used to explore the risk factors for AMS. Results: The age of the participants was (36.1±10.5) years old at baseline, and 95.27% (10 438) of them were males. The follow-up time was (17.46±4.23) months. The altitude of the residence place in early-life and working environment were (1 959±937) m and (4 533±233) m, respectively. During the follow-up period, the incidence of AMS was 15.58% (1 707 cases), and the incidence for acute mountain sickness and high altitude pulmonary edema were 15.53% (1 702 cases) and 0.05% (5 cases), respectively. No high altitude cerebral edema patients were found. Cox proportional hazards model showed that the risk of AMS increased by 45% for every 100 m elevation in the altitude of working environment [HR (95%CI): 1.45 (1.41-1.51)]. The higher the altitude for the residence place in early-life, the lower the risk of AMS [HR (95%CI): 0.84 (0.80-0.88)]. Compared with the group with oxygen saturation during 90%-94%, the participants with oxygen saturation<75% [HR (95%CI): 1.67 (1.24-2.23)] at baseline was also associated with increased risk of AMS. Conclusions: The incidence of AMS is relatively low in grid construction workers working on plateau. The risk factors of AMS included higher working altitude, lower altitude of the residence place in early-life and oxygen saturation<75%.

[Current situation and trend of medical laboratory results homogeneity management].

Medical test results are indispensable and important tools in diagnosis and treatment services. It is necessary to promote the homogenization of test results first, because homogenization is the basis for mutual recognition of test results. Mutual recognition of medical test results can help share resources among medical institutions, provide more reliable test results for early prevention, screening and treatment of diseases, and reduce repeated tests, thus improving people's medical experience. In recent years, with the deepening of medical system reform and the promotion of graded diagnosis and treatment, governments have continuously introduced policies of mutual recognition of test results around country. However, homogenization is a prerequisite for mutual recognition of test results, with the emergence of intelligent medicine in the era of internet big data, opportunities and challenges coexist in the development of homogeneity management. In the future, the homogeneity of medical test results will present a trend of digitalization, automation, informatization and intelligence.

[Molecular epidemiological study on rubella virus circulating in Yunnan Province during 2011-2021].

Objective: To understand the genotype distribution and transmission pattern of rubella virus (RuV) circulating in Yunnan Province. Methods: Throat swab samples were collected from rubella outbreaks and sporadic cases in nine prefectures/cities of Yunnan Province from 2011 to 2021. Virus isolation, amplification of target genes and sequence determination were performed on the RuV-positive samples. The genotypes and lineages of Yunnan strains were determined by comparing them with the reference strains, and further phylogenetic analysis was performed with Yunnan strains and strains circulating in other provinces of China during the same period. Results: RuV circulating in Yunnan province during 2011-2021 showed significant genetic diversity, and three lineages, 1E-L1, 2B-L1 and 1E-L2, were detected. Two lineage-switches were also identified, including the conversion of 1E-L1 to 2B-L1 between 2012 and 2013, and the replacement of 2B-L1 to 1E-L2 after 2018. The time of the switches was basically consistent with the outbreak in Yunnan province in 2012 and the time of the rubella reemergence and epidemic between 2018 and 2019. The amino acid sequence of RuV virus strains in Yunnan province was highly conserved, and no important functional regions were changed. Conclusions: The transmission pattern of RuV in Yunnan province is generally consistent with the epidemic trend of RuV in other provinces of China.

[Primary hepatic angiosarcoma: a clinicopathological analysis of nine cases].

Objective: To investigate the clinical manifestations, histomorphology, and differential diagnosis of primary hepatic angiosarcoma. Methods: Nine cases of primary hepatic angiosarcoma diagnosed in the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from January 2014 to December 2021 were collected, including biopsy and surgical specimens. The histomorphology, clinical, and radiologic findings were analyzed. The relevant literature was also reviewed. Results: There were six males and three females, aged 30 to 73 years (mean 57 years). Grossly, the growth pattern of the tumor was classified as either mass formation or non-mass formation (sinusoidal). Microscopically, the mass-forming primary hepatic angiosarcoma were further subdivided into vasoformative or non-vasoformative growth patterns; and those non-vasoformative tumors had either epithelioid, spindled, or undifferentiated sarcomatoid features. Sinusoidal primary hepatic angiosarcoma on the other hand presented with markedly dilated and congested blood vessels of varying sizes, with mild to moderately atypical endothelial cells. Follow-up in all nine cases revealed 8 mortality ranging from 1 to 18 months (mean 5 months) from initial diagnosis. One patient was alive with disease within a period of 48 months. Conclusions: Primary hepatic angiosarcoma is a rare entity with a wide spectrum of histomorphology, and often misdiagnosed. It should be considered when there are dilated and congested sinusoids, with overt nuclear atypia. The overall biological behavior is aggressive, and the prognosis is worse.

[Malignant peripheral nerve sheath tumor: a clinicopathological analysis].

Objective: To investigate the clinicopathological, immunophenotypic, and genetic features of malignant peripheral nerve sheath tumor (MPNST). Methods: Twenty-three cases of MPNST were diagnosed at the Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University), China, between January 2012 and December 2022 and thus included in the study. EnVision immunostaining and next-generation sequencing (NGS) were used to examine their immunophenotypical characteristics and genomic aberrations, respectively. Results: There were 10 males and 13 females, with an age range of 11 to 79 years (median 36 years), including 14 cases of neurofibromatosis type I-associated MPNST and 9 cases of sporadic MPNST. The tumors were located in extremities (7 cases), trunk (4 cases), neck and shoulder (3 cases), chest cavity (3 cases), paraspinal area (2 cases), abdominal cavity (2 cases), retroperitoneum (1 case), and pelvic cavity (1 case). Morphologically, the tumors were composed of dense spindle cells arranged in fascicles. Periphery neurofibroma-like pattern was found in 73.9% (17/23) of the cases. Under low magnification, alternating hypercellular and hypocellular areas resembled marbled appearance. Under high power, the tumor cell nuclei were irregular, presenting with oval, conical, comma-like, bullet-like or wavy contour. In 7 cases, the tumor cells demonstrated marked cytological pleomorphism and rare giant tumor cells. The mitotic figures were commonly not less than 3/10 HPF, and geographic necrosis was often noted. Immunohistochemically, tumor cells were positive for S-100 (14/23, 60.9%) and SOX10 (11/23, 47.8%). The loss of the CD34-positive fibroblastic network encountered in neurofibromas was observed in 14/17 of the MPNST cases. The loss of H3K27me3 expression was observed in 82.6% (19/23) of the cases. Moreover, SDHA and SDHB losses were presented in one case. NGS revealed that NF1 gene loss of function (germline or somatic) were found in all 5 cases tested. Furthermore, four cases accompanied with somatic mutations of SUZ12 gene and half of them had somatic mutations of TP53 gene, while one case with germline mutation in SDHA gene and somatic mutations in FAT1, BRAF, and KRAS genes. Available clinical follow-up was obtained in 19 cases and ranged from 1 to 67 months. Four patients died of the disease, all of whom had the clinical history of neurofibromatosis type Ⅰ. Conclusions: MPNST is difficult to be differentiated from a variety of spindle cell tumors due to its wide spectrum of histological morphology and complex genetic changes. H3K27me3 is a useful diagnostic marker, while the loss of CD34 positive fibroblastic network can also be a diagnostic feature of MPNST. NF1 gene inactivation mutations and complete loss of PRC2 activity are the common molecular diagnostic features, but other less commonly recurred genomic aberrations might also contribute to the MPNST pathogenesis.

[The relationship between insulin resistance and risk of long-term mortality in people without diabetes: a 30-year follow-up of the Daqing Diabetes Study].

Objective: To determine whether insulin resistance is associated with all-cause mortality in subjects without diabetes. Methods: A total of 505 participants without diabetes, 198 with normal glucose tolerance (NGT) and 307 with impaired glucose tolerance (IGT), were recruited from the Daqing Diabetes Study. The participants were followed up for 30 years. They were stratified into three groups (tertiles) according to baseline homeostasis model assessment of insulin resistance(HOMA-IR) levels, as the HOMA-IR 0, the HOMA-IR 1 and the HOMA-IR 2 groups, to assess the predictive effect of insulin resistance on risk of all-cause mortality. Results: During the 30-year follow-up, 52, 56 and 78 participants died across the three HOMA-IR groups, respectively. The corresponding mortality per 1 000 person-years (95%CI) were 12.12 (9.56-15.01), 13.10 (10.46-16.03) and 19.91 (16.73-23.15), respectively. Participants in the HOMA-IR 2 group had a significantly higher risk of death than those in the HOMA-IR 0 group after adjustment of age, sex and smoking status (HR=1.97,95%CI 1.38-2.81, P<0.001). Cox analyses showed that a one standard deviation increase in HOMA-IR was associated with a 22% increase in the mortality after adjustment of potential confounders (HR=1.22, 95%CI 1.08-1.39, P=0.002). Conclusions: Insulin resistance is associated with increased risk of all-cause death in Chinese people without diabetes, suggesting that improving insulin resistance could be beneficial for people without diabetic in reducing risk of long-term all-cause mortality.

[CIC-rearranged sarcoma with rhabdoid features: a clinicopathological analysis].

Objective: To investigate the histopathologic, immunohistochemical, molecular genetic characteristics of CIC-rearranged sarcoma (CRS) with rhabdoid features. Methods: The clinical and pathologic data of two cases of CRS diagnosed between 2019 and 2021 at the Department of Pathology, Jiangsu Province Hospital were analyzed. Immunohistochemical study and fluorescence in situ hybridization (FISH) were performed. The relevant literature was reviewed. Results: Both patients were female, one was 58 years old, with tumor located in left thigh; the other was 43 years old, with tumor located in left pelvic cavity. Microscopically, both tumors were composed of small to medium-sized round, oval cells, arranged in nodules or sheets. The tumor cells showed irregular nuclear outline, coarse chromatin with prominent nucleoli and brisk mitotic activity. Both cases showed rhabdoid phenotype with myxoid stromal changes. Immunohistochemically, both cases were positive for CD99 and c-myc. High WT1 reactivity was seen in classic area, with low reactivity in rhabdoid area. There was no INI1 lost in both cases. Both were negative for NKX2.2 and NKX3.1. By FISH both cases demonstrated convincing break-apart signals of CIC gene. One patient died of disease after 1 month, and the other died of disease after 3 months. Conclusions: CRS is a small round cell undifferentiated sarcoma of the bone and soft tissue defined by molecular genetic characteristics, and may show atypical morphologic and immunophenotypic characteristics such as rhabdoid features. A correct understanding of its rare morphologic and immunophenotypic characteristics, combined with molecular pathologic detection, is conducive to correct diagnosis.

[Investigation and analysis of occupational hazards in construction of power transmission and transformation project].

Objective: To investigate the occupational hazard factors and exposure levels of workers during the construction of power transmission and transformation projects. Methods: Analysis and identification of occupational hazard factors were carried out for typical construction process of 6 power transmission projects and 3 substation projects in September 2018. The on-site occupational health investigation was carried out to detect and analyze the exposure levels of workers to occupational hazard factors. Results: The time weighted average concentration (C(TWA)) of crushing workers exposed to silica dust and welders exposed to welding fume in substation projects were 2.72 and 14.03 mg/m(3), respectively. The 8 h equivalent sound level results of exposure noise of carpenters in power transmission projects and crushing workers, reinforcement workers, carpenters, scaffolders, road builders in substation projects were 87.9, 92.5, 87.1, 92.5, 93.0 and 90.2 dB (A) , respectively. The 4-hour time equal energy frequency weighted vibration acceleration of hand-transmitted vibration of bricklayer in power transmission projects, bricklayer, general worker 3, road builder 1 and road builder 2 of substation projects were 5.36, 5.21, 5.28, 10.71 and 5.22 m/s(2), respectively. The effective irradiance of electric welding arc light of welders' limbs in power transmission projects and substation projects were 401.19, 319.68 µW/cm(2), respectively. All of the above exceeded the requirements of occupational exposure limits. The occupational radiation levels and exposure limits of hazardous chemical factors met the requirements of each post. Conclusion: During the construction of power transmission and transformation projects, the exposure levels of occupational hazard factors in multiple posts exceed the standard. The main responsibility of employers for occupational disease prevention and control should be implemented, and targeted comprehensive measures should be taken to reduce the exposure levels of occupational hazard factors of workers.

[Clinicopathological features of inflammatory myofibroblastic tumor].

Objective: To investigate the clinicopathological diagnosis and differential diagnosis of inflammatory myofibroblastic tumor (IMT). Methods: Thirty-two cases of IMT collected at the People's Hospital of Jiangsu Province from May 2010 to May 2020 were evaluated for their clinical, histologic, immunohistochemical and genomic features, and relevant literature was reviewed. Results: There were 19 male and 13 female patients, with age ranging from 5 to 65 years (mean, 37 years). The tumors were located in the lung and mediastinum (10 cases), gastrointestinal tract and mesentery/omentum (12 cases), urinary bladder (5 cases), head and neck (3 cases), somatic soft tissue (1 case), and retroperitoneum (1 case). Four cases of epithelioid inflammatory myofibroblastic sarcoma (EIMS) were all located intra-abdominally. Histologically, the tumor cells were myofibroblasts and fibroblasts arranged in predominantly fusiform pattern, with variably edematous to myxoid background or sclerotic collagenized stroma, and variably mixed chronic or acute inflammatory cells infiltration. EIMS were composed mainly of epithelioid tumor cells, with myxoid stroma and numerous neutrophils. Immunohistochemically, the tumor cells expressed cytoplasmic ALK (25/32, 78%), whereas the four EIMS showed nuclear membrane ALK staining pattern. The tumor cells also expressed CKpan (8/19), SMA (24/32, 75%) and desmin (12/32, 38%); all four EIMS also showed strong positivity for desmin. Fluorescence in situ hybridization (FISH) for ALK gene rearrangement showed split apart signals in 12 of 15 cases, most commonly with atypical signals. Next-generation sequencing (NGS) was performed in three tumors and showed that one case of lower leg IMT harbored a novel CLIP2-ALK fusion, and two cases of EIMS harbored RANBP2-ALK fusion. Follow-up data were available in 29 patients. Twenty-two patients were alive with no evidence of tumor, four patients had tumor recurrences (three patients were treated with crizotinib and were alive with tumor), and three patients died of the disease (including two patients with EIMS). Conclusions: IMTs show a wide morphologic spectrum, and should be differentiated form a variety of benign or malignant tumors. Immunohistochemistry (ALKp80, ALKD5F3) and FISH (ALK break-apart probe) could assist the diagnosis of IMT, with NGS recommended for the atypical cases.

[Epithelioid hemangioendothelioma with TFE3 translocation in soft tissue:a clinicopathological study].

Objective: To investigate the clinicopathological and molecular features, diagnosis and differential diagnosis of TFE3-rearranged epithelioid hemangioendothelioma (EHE). Methods Two cases of TFE3-rearranged EHE arising from soft tissues, diagnosed by the Pathology Department of the First Affiliated Hospital of Nanjing Medical University from 2013 to 2020 were observed. EnVision method was used for immunophenotyping, fluorescence in situ hybridization (FISH) was used to test TFE3 gene rearrangements and WWTR1-CAMTA1 fusion gene,and next-generation sequencing (NGS) was used to delineate the fusion transcripts. Results: Details of these two cases were as follows: case 1, male, 51 years old, with tumor in the right temporal region; case 2, female, 42 years old, with tumor in the right neck. The tumors showed progressive painless enlargement. Grossly, the tumor of case 1 was multinodular with unclear boundary and grayish red cut surface, while the tumor of case 2, originating from a vein, appeared as a firm, tan mass within vessel wall. Microscopically, both tumors showed moderate cellularity and were consisted of plump, epithelioid, or histiocytoid cells with eosinophilic cytoplasm and mild-to-moderate nuclear pleomorphism. Most of the tumor cells were arranged in solid or alveolar growth patterns, while some tumor cells showed intraluminal papillary growth pattern in case 1 and anastomosing vascular channels and extramedullary hematopoiesis in case 2. Immunohistochemically, the tumor cells showed diffuse positivity for CD31, CD34, ERG, and TFE3. FISH revealed TFE3 break-apart signals in two cases, but WWTR1-CAMTA1 gene fusion was not detected. NGS identified YAP1 (exon1)-TFE3 (exon6) fusion gene in case 2. Clinical follow-up information was available in both cases for a follow-up period of 15 and 59 months respectively. Patient 1 had a relapse 22 months after surgery, and was currently alive with the tumor. Patient 2 remained disease-free. Conclusions: TFE3-rearranged EHE is a rare molecular subtype of EHE, with accompanying characteristic morphologic features. However the morphologic spectrum remains under-recognized, and more experience is needed. Immunohistochemical and molecular examinations are helpful for the diagnosis and differential diagnosis of the disease.

Application of Sarcosaprophagous Insects to Estimate the Postmortem Interval in 11 Cases.

ABSTRACT: Objective To test the feasibility and accuracy of with sarcosaprophagous insects postmortem interval （PMI） estimation with sarcosaprophagous insects and provide references for estimation practice. Methods Eleven cases confirmed by the detection results, with complete entomological evidence were selected. The insect species, estimation results and true results involved in the cases were statistically analyzed and compared. Results Thirteen species of insects were found at the criminal scene, including Chrysomya megacephala （Fabricius）, Chrysomya rufifacies （Macquart）, Chrysomya nigripes （Aubertin）, Lucilia sericata （Meigen）, Hydrotaea spinigera Stein, Muscina stabulans （Fallén）, Sarcophagid （species were not identified）, Megaselia scalaris （Loew）, Hermetia illucens （Linnaeus）, Saprinus splendens （Paykull）, Creophilus maxillosus （Linnaeus）, Dermestes maculatus （De Geer） and Necrobia ruficollis （Fabricius）. The PMI of all eleven cases was within the range of estimated PMI. The estimated results of 72.73% cases were on the same day of the true results. Conclusion Sarcosaprophagous insects can estimate the PMI simply and conveniently. In cases where the PMI is within the time range of one generation of flies or beetles, the estimation results are relatively accurate. However, the estimation is less accurate when the PMI is beyond the time range.

Multivariate classification of earthquake survivors with post-traumatic stress disorder based on large-scale brain networks.

OBJECTIVE: The identification of post-traumatic stress disorder (PTSD) among natural disaster survivors is remarkably challenging, and there are no reliable objective signatures that can be used to assist clinical diagnosis and optimize treatment. The current study aimed to establish a neurobiological signature of PTSD from the connectivity of large-scale brain networks and clarify the brain network mechanisms of PTSD. METHODS: We examined fifty-seven unmedicated survivors with chronic PTSD and 59 matched trauma-exposed healthy controls (TEHCs) using resting-state functional magnetic resonance imaging (rs-fMRI). We extracted the node-to-network connectivity and obtained a feature vector with a dimensionality of 864 (108 nodes × 8 networks) to represent each subject's functional connectivity (FC) profile. Multivariate pattern analysis with a relevance vector machine was then used to distinguish PTSD patients from TEHCs. RESULTS: We achieved a promising diagnostic accuracy of 89.2% in distinguishing PTSD patients from TEHCs. The most heavily weighted connections for PTSD classification were among the default mode network (DMN), visual network (VIS), somatomotor network, limbic network, and dorsal attention network (DAN). The strength of the anticorrelation of FC between the ventral medial prefrontal cortex (vMPFC) in DMN and the VIS and DAN was associated with the severity of PTSD. CONCLUSIONS: This study achieved relatively high accuracy in classifying PTSD patients vs. TEHCs at the individual level. This performance demonstrates that rs-fMRI-derived multivariate classification based on large-scale brain networks can provide potential signatures both to facilitate clinical diagnosis and to clarify the underlying brain network mechanisms of PTSD caused by natural disasters.

A radiomics-clinical nomogram for preoperative prediction of IDH1 mutation in primary glioblastoma multiforme.

AIM: To develop and validate an individualised radiomics-clinical nomogram for the prediction of the isocitrate dehydrogenase 1 (IDH1) mutation status in primary glioblastoma multiforme (GBM) based on radiomics features and clinical variables. MATERIALS AND METHODS: In a retrospective study, preoperative magnetic resonance imaging (MRI) images were obtained of 122 patients with primary glioblastoma (development cohort = 101; validation cohort = 21). Radiomics features were extracted from total tumour based on the post-contrast high-resolution three-dimensional (3D) T1-weighted MRI images. Radiomics features were selected by using a least absolute shrinkage and selection operator (LASSO) binomial regression model with nested cross-validation. Then, a radiomics-clinical nomogram was constructed by combining relevant radiomics features and clinical variables and subsequently tested by using the independent validation cohort. RESULTS: A total of 105 features were quantified on the 3D MRI images of each patient, and eight were selected to construct the radiomics model for predicting IDH1 mutation status. The mean classification accuracy and mean κ value achieved with the model were 88.4±3% and 0.701±0.08, respectively. The radiomics-clinical nomogram, which combines eight radiomics features and three clinical variables (patient age, sex and tumour location), demonstrated good discrimination (C-index 0.934 [95% CI, 0.874 to 0.994]; F1 score 0.78) and performed well with the validation cohort (C-index 0.963 [95% CI, 0.957 to 0.969]; F1 score 0.91; AUC 0.956). CONCLUSIONS: A radiomics-clinical nomogram was developed and proved to be valuable in the non-invasive, individualised prediction of the IDH1 mutation status in patients with primary GBM. The nomogram can be applied using clinical conditions to facilitate preoperative patient evaluation.

[Clinicopathological significance of cyclin D1 expression in Rosai-Dorfman disease].

Objective: To study the clinicopathological significance of cyclin D1 expression in Rosai-Dorfman disease (RDD). Methods: Seventeen cases of RDD were evaluated by HE, immunohistochemical staining and molecular genetic analysis. Expression of cyclin D1 was compared between RDDs and control group that included 29 cases of reactive histiocytosis, 9 cases of IgG4-related disease, and 2 cases of Erdheim-Chester disease. Results: Cyclin D1 was expressed in RDDs (17/17), reactive histiocytosis (11/29), IgG4-related diseases (3/9), and Erdheim-Chester disease (2/2), respectively, with nuclear staining in the RDD cells or proliferative histiocytes. Chi-square test showed that expression of cyclin D1 was significantly higher in RDDs than in reactive histiocytosis and IgG4-related diseases (P<0.01), but not in Erdheim-Chester diseases (P>0.05). The expression threshold for recalculating the percentage of cyclin D1 positive cells was 27.5% (AUC=0.981, P<0.01) by ROC curve. However, CCND1 gene had no rearrangement detected by fluorescence in situ hybridization, but with increased copies of gene in some RDD cells. ARMS-PCR analysis also did not detect KRAS, BRAF and NRAS gene mutations in any cases. Conclusions: Cyclin D1 may serve as an additional diagnostic marker for RDDs. Its high expression may be related to activation of MAPK pathway, but the pathogenetic significance of cyclin D1 in RDDs needs further study.

[Clinicopathological study of large B-cell lymphoma with IRF4 rearrangement].

Objective: To study the clinicopathological features of large B-cell lymphoma (LBCL) with IRF4 rearrangement. Methods: Seven cases of LBCL with IRF4 rearrangement collected at the First Affiliated Hospital of Nanjing Medical University from November 2018 to October 2019 were evaluated by hematoxylin and eosin staining, immunohistochemistry and fluorescence in situ hybridization detection. The relevant literature was reviewed. Results: Four tumors were located in the tonsils, 2 tumors in the lymphoid nodes and one tumor in the adenoid.The patients were 3 males and 4 females patients with a median age of 24 years (range, 6 to 39 years).Microscopically, entirely follicular pattern was present in one case, entirely diffuse pattern in 2 cases, and follicular and diffuse pattern in other 4 cases. The tumor cells were medium to large in size and showed the morphology of centroblasts or blastoid cells with irregular nuclei, brisk mitotic activity in 3 cases and starry sky in 2 cases. All of the cases were positive for CD20, PAX-5, bcl-6, and MUM1 and had a Ki-67 index>80%, while CD10 and bcl-2 were positive in 3 cases. IRF4 gene rearrangement was identified in all cases and bcl-6 gene rearrangement in 2 cases. All patients presented with localized disease with clinical stage Ⅰ or Ⅱ, except one with stage Ⅳ at presentation and a new lesion in the mediastinum developed 8 months later. Conclusions: LBCL with IRF4 rearrangement is a clinicopathologically distinct entity. The observations reveal a broader spectrum of morphology and biological behaviors. The relationship between clinical stage and prognosis needs to be determined in more cases.

[Pulmonary artery intimal sarcoma: a clinicopathological analysis of three cases].

Objective: To investigate the clinicopathological characteristics, genetic features, diagnosis and differential diagnosis of pulmonary artery intimal sarcoma (PAIS). Methods: Three cases of PAIS were collected from Jiangsu Province People's Hospital (from February 2016 to November 2019). The clinical data, imaging examination, morphology, immunostaining, and molecular changes were retrospectively analyzed. Results: There were 1 male and 2 females (age: 32, 50, 60 years), who had symptoms of cough, asthma or chest tightness. Imaging findings indicated low density filling defects which were suspected as thrombus, embolism or myxoma. Grossly, the main tumor was located in the elastic arteries and their lobar branches, also extended into the atrium and ventricle, with lung parenchymal infiltration focally. Microscopically, tumor cells were predominantly composed of abundant spindle cells with obvious atypia and myxoid background, resembling fibroblastic or myofibroblastic differentiation. Active mitotic figures and necrosis could be seen in some areas. Immunohistochemical staining of vimentin was strongly positive, while pan-cytokeratin, S-100, desmin, Fli-1, CD31, SMA and ERG etc were variably positive only in focal areas. FISH detection showed amplification of MDM2 gene in three cases and EGFR gene in two cases. Metastatic lesions were found in one case by 18, 32 and 42 months after surgery respectively. There was no recurrence or metastasis in the other two cases. Conclusions: PAIS is one of exceptionally poor differentiated mesenchymal tumor that arises from the arterial intima of elastic pulmonary arteries. There was no definite differention in morphology. Gene detection shows amplification of MDM2 and EGFR gene. This tumor often has poor prognosis with aggressive behavior. Complete resection is the only effective therapeutic option. There is disagreement as to whether chemotherapy and radiotherapy can improve survival.