[Clinical analysis of cytomegalovirus infection-associated hemophagocytic lymphohistiocytosis in five patients without underlying diseases].

The clinical data of five patients [one male and four female; median age: 31 (21-65) years] with cytomegalovirus (CMV)-induced hemophagocytic lymphohistiocytosis (HLH) diagnosed and treated in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed from January 2011 to December 2020. None of the patients had any underlying disease, and all were immunocompetent. The main clinical presentations were fever in all five patients, splenomegaly in four, enlarged lymph nodes in two, liver enlargement in one, and rash in three. Pulmonary infection was found in three patients, two of whom developed respiratory failure. Two patients had jaundice. Central nervous system symptoms and gastrointestinal bleeding were observed in one case. All patients received glucocorticoids and antiviral therapy. One patient was treated with the COP (cyclophosphamide+vincristine+prednisone) chemotherapy regimen after antiviral therapy failed and he developed central nervous system symptoms. After treatment, four patients achieved remission, but the fifth pregnant patient eventually died of disease progression after delivery. CMV-associated HLH in an immunocompetent individual without underlying diseases is extremely rare, and most patients have favorable prognosis. Antiviral therapy is the cornerstone of CMV-HLH treatment.

[The development and future of sports medicine in China].

This article mainly introduces the development history and current situation of sports medicine in China, and deeply analyzes the problems that have emerged during the current development process, and proposes corresponding solutions. Based on this, the article proposes five key directions for the development of sports medicine, which are: developing arthroscopic minimally invasive techniques, ensuring the guarantee work for competitive sports, attaching great importance to the development of sports rehabilitation, vigorously carrying out exercise prescription and exercise assessment work, and emphasizing the training and education of sports medicine professionals. Finally, the article looks forward to the future development of sports medicine from three aspects: popularizing and expanding the influence of sports medicine through popular science promotion, improving the quality and safety of sports through health management and disease prevention, and achieving precise diagnosis and treatment through scientific research and innovation. It is hoped that this article will provide reference for the development of sports medicine in China.

[Analysis of clinical effect of arthroscopic release at different time in treating knee adhesion after arthroscopic surgery].

Objective: To explore the efficacy of arthroscopic release in treating postoperative knee adhesion and investigate the influence of release timing on the treatment outcomes. Methods: A total of 50 patients who accepted arthroscopic release in Peking University Third Hospital from February 2017 to December 2021 were included in the retrospective cohort. The study cohort comprised 28 men and 22 women, with a mean age of (30.8±11.9) years. All the primary surgeries were manipulated under arthroscopes. A comparison was made between pre-and postoperative range of motion (ROM), visual analog scale (VAS), International Knee Documentation Committee (IKDC) scores, and Tegner activity scale scores for the patients. According to the interval between the appearance of adhesion and arthroscopic release, the patients were divided into four groups:<3 months group (n=12), 3-6 months group (n=16),>6-12 months group (n=14), and>12 months group (n=8). Inter-group comparisons on postoperative ROM, IKDC scores, and Tegner activity scale scores and improvement values of each outcome were conducted. Results: All the patients were followed up for (36.4±19.7) months. Patients gained significant improvement in flexion, extension, IKDC scores, and Tegner scores (125.0°±20.0° vs 75.7°±27.5°, 2.3°±4.8° vs 7.4°±7.3°, 69.8±17.7 vs 51.4±12.8, 4.1±2.1 vs 2.2±1.1) (all P<0.05), while the VAS scores did not show significant improvement. There were no significant differences among different groups in postoperative extension, IKDC scores or Tegner scores, nor in their improvements. However, patients in the ≤6 months group could gain better postoperative flexion and improvement in flexion than those in the >6 months group (129.9°±20.0° vs 118.8°±17.4°, 58.6°±32.8° vs 37.3°±23.1°) (P<0.05). Conclusions: Arthroscopic release presents a great effect in treating knee adhesion after arthroscopic operation. Once the symptoms of adhesion appear and physical rehabilitation fails to improve the ROM, one should accept early surgical intervention (less than 6 months) for a better outcome.

[Primary pulmonary NUT carcinoma: a clinicopathological analysis of seven cases].

Objective: To investigate the clinicopathological characteristics of primary pulmonary NUT carcinoma. Methods: A total of 7 cases of primary pulmonary NUT carcinoma were collected from Fujian Provincial Hospital (n=5), Fuzhou Taijiang Hospital (n=1) and Binzhou City People's Hospital of Shandong Province (n=1) from January 2021 to April 2023. The clinical, histopathological, and immunohistochemical features were analyzed, and NUT rearrangement were detected by fluorescence in situ hybridization (FISH) with break-apart probes. Results: Seven cases were all male with age ranging from 32 to 73 years. The main clinical manifestations were cough, expectoration and chest tightness. Microscopically, NUT carcinoma was composed of monotonous proliferation of primitive-appearing small-to-medium round cells, with few eosinophilic cytoplasm, arranged in solid sheets, nests or clusters. Abrupt keratinization was typically observed in 4 cases (4/7), with high mitotic activities and necrosis. Immunohistochemistry (IHC) showed that the tumors were positive for NUT (7/7), CK7 (4/4), CK5/6 (5/6), p40 (6/7). Ki-67 index were 30%-80%. NUT gene segregation (7/7) was detected by FISH break probes. Conclusions: Primary pulmonary NUT carcinoma is rare and highly malignant. Diagnosis depends on histopathology and IHC, with molecular detection as an adjunct for diagnosis. Pathologists should be aware of the clinicopathological characteristics to avoid misdiagnosis.

[Myxiod pleomorphic liposarcoma: a clinicopathological and molecular genetic analysis of six cases].

Objective: To investigate the clinicopathologic and molecular genetic characteristics of myxoid pleomorphic liposarcoma (MPLPS). Methods: Six cases of MPLPS diagnosed and consulted in Fujian Provincial Hospital from 2015 to 2021 were collected for histomorphological observation, immunohistochemistry, and fluorescence in situ hybridization (FISH) detection of DDIT3 (CHOP) gene translocation and MDM2/CDK4 gene amplification. Results: There were four males and two females, aged 26-74 years (mean 53.8 years). The tumor size was 3.8-16.0 cm (mean 11.8 cm). All six cases had similar histopathologic features, showing overlapping histologic morphology of myxoid liposarcoma and pleomorphic liposarcoma. Four cases (4/6) were positive for S-100 protein, and the Ki-67 index was 50%-95%. All cases (6/6) were negative for DDIT3 (CHOP) translocation and MDM2/CDK4 amplification by FISH. TP53 (p.R248w) germline mutation was found in one case. Conclusions: MPLPS is a rare subtype of liposarcoma, characterized by overlapping morphology of myxoid liposarcoma and pleomorphic liposarcoma. Genetically, a few of them have TP53 gene germline mutations, but they lack of DDIT3 (CHOP) translocation or MDM2/CDK4 amplification.

Insight into different host range of three planthoppers by transcriptomic and microbiomic analysis.

Brown planthopper (BPH), white-backed planthopper (WBPH) and small brown planthopper (SBPH), are the closely related rice pests that perform differentially on wheat plants. Using fecundity as a fitness measure, we found that SBPH well-adapted on wheat plants, followed by WBPH, while BPH had the worst performance. The transcriptomic responses of SBPH and BPH to wheat plants have been compared previously. To understand the different fitness mechanisms of three planthoppers, this study first investigated the transcriptomic responses of WBPH to rice and wheat plants. Genes involved in detoxification, transportation and proteasome were significantly enriched in WBPH in response to different diets. Moreover, comparative analysis demonstrated that most co-regulated genes in BPH and SBPH showed different expression changes; whereas most co-regulated genes in BPH and WBPH exhibited similar expression changes. Subsequently, this study also investigated the influences of host plants on the bacterial community of three planthoppers. The three planthoppers harboured distant diversity of bacterial communities. However, there was no dramatic change in bacterial diversity or relative abundance in planthoppers colonized on different hosts. This study illustrates generic and species-specific changes of three rice planthoppers in response to different plants, which deepen our understanding towards the host fitness for planthopper species.

[Clinical efficacy of the combined diagnosis and management for children with airway allergic diseases].

Objective: To evaluate the clinical efficacy of the combined diagnosis and management in children with airway allergic diseases(bronchial asthma, allergic rhinitis). Methods: This observational study belongs to cluster sampling cases, which included the clinical data from children with airway allergic diseases in Allergy Department and Otorhinolaryngology Department of Beijing Children's Hospital from April to December in 2015. They were followed up every three months during 12 months. All the subjects were required to continuously record daily symptom by diary card. ACT/c-ACT, VAS, treatment steps to control asthma, respiratory infections, wheeze, pulmonary function(FEV1%pred,FEV1/FVC,PEF%pred,FEF25%pred,FEF50%pred,FEF75%pred,MMEF%pred), FeNO were assessed in every visiting. The mean±standard deviation was used for the measurement data in accordance with normal distribution. Comparing the pulmonary function indexes at every point, the measurement data with normal distribution and uniform variance were analyzed by single factor analysis of variance, and the measurement data with uneven variance were tested by non-parametric rank sum test. Results: Among 147 recruited participants, 106 completed the combined diagnosis and management. The airway allergic diseases control rate was 87.7% at 12 months after the combined diagnosis and management. At every point, the average daily symptom score and VAS score which were significantly lower than at the baseline(H=35.854,P=0.000)[ 1.2(0.7,2.2),0.6(0.2,1.5),0.4(0.1,1.0),0.5(0.1,1.1) vs 2.0(1.0,3.5)],(H=39.559,P=0.000)[2.5(0.5,4.7),2.2(0.3,4.4),1.8(0.2,4.6),1.6(0.3,3.8) vs 6.9(4.1,9.8)]. ACT/c-ACT score at 3, 6, 9, 12 months were significantly higher than at the baseline (H=79.695,P=0.000) [25.0(22.5,27.0),26.0(24.0,27.0),25.0(23.0,27.0),25.0(24.0,27.0) vs 20.0(17.0,22.0)]. FEV1%pred and FEF25%pred at 3, 6 months were significantly higher than at the baseline (F=3.563,P=0.007)(104.7±12.6 vs 96.8±14.5,103.0±10.3 vs 96.8±14.5),(F=2.456,P=0.046)(96.6±22.0 vs 85.0±21.9,93.3±18.0 vs 85.0±21.9). PEF%pred at 3, 6, 9, 12 months after the combined diagnosis and management were significantly higher than at the baseline(F=5.497,P=0.000)(105.1±18.1,101.2±15.3,99.7±17.1,99.8±17.5 vs 90.3±17.8). FeNO at 3, 6, 9, 12 months respectively were no significantly differences at the baseline(F=0.751,P=0.558)(25.7±23.6 vs 30.7±25.6,25.9±16.5 vs 30.7±25.6,27.5±20.2 vs 30.7±25.6,30.6±19.6 vs 30.7±25.6).The respiratory infections rate were 69.8%(74/106),67.0%(71/106),60.4%(64/106),51.9%(55/106) at 3, 6, 9, 12 months respectively. The wheezing rate was 24.5%(26/106),14.2%(15/106),11.3%(12/106),7.5%(8/106) at 3, 6, 9, 12 months respectively. Conclusions: The combined diagnosis and management can significantly improve the control level of children's airway allergic diseases, which should be implemented in the management of children's airway allergic diseases.

[Clinicopathological analysis of clear cell renal cell carcinoma with hemangioblastoma component].

Objective: To investigate the clinicopathological features, differential diagnosis and molecular characteristics of clear cell renal cell carcinoma (ccRCC) with hemangioblastoma component (ccRCC-HBc). Methods: Two ccRCC-HBc cases diagnosed at Fujian Provincial Hospital in September 2015 and March 2016, respectively, were included. Their morphological, immunohistochemical and molecular features were analyzed, including fluorescence in situ hybridization (FISH) detection of TFE3, TFEB and VHL genes. Related literature was reviewed to reveal the characteristics of this tumor. Results: The two cases occurred in 2 women, aged 33 and 66 years, respectively. The maximum diameters of the tumors were 4.0 cm and 8.5 cm, respectively. Histologically, the ccRCC component, representing approximate 10%-20% of the neoplasm, while the tumor cells arranged in flaky, nested, and solid distribution. The tumor cells had conspicuous nucleoli, with rich thin-wall capillary network in the stroma. The hemangioblastoma-like component, representing approximate 60%-70% of the neoplasm, showed a rich capillary network of single-layered flat endothelial cells enclosing stromal cells. The latter cell type showed a pale or eosinophilic cytoplasm exhibiting occasional lipid droplets. Rare cell nuclei appeared enlarged, pleomorphic, or bizarre. The two components were intermingled with each other. Immunohistochemically, the tumor cells were positive for PAX8, CKpan, EMA, vimentin, CD10, RCC, CAⅨ, and P504s in ccRCC area; in another area, the tumor cells were positive for α-inhibin, CD34 and vimentin, while CD10 were weakly positive. Neither TFE3 or TFEB gene split signal was detected in the 2 cases (0/2), nor was VHL gene mutation in case 2 (0/1). Conclusion: ccRCC-HBc is an extremely rare entity of ccRCC. The diagnosis is mainly based on clinical and pathological characteristics, as well as immunohistochemistry. Molecular pathology is helpful for its differential diagnosis. The primary approach of treating ccRCC-HBc is complete surgical excision and chemotherapy. The targeted treatment is helpful if possible.

[Clinicopathological features of gastric adenocarcinoma with enteroblastic differentiation: a report of twelve cases].

Objective: To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of gastric adenocarcinoma with enteroblastic differentiation (GAED). Methods: Twelve cases of GAED diagnosed in Fujian Provincial Hospital from August 2019 to August 2020 were collected. HE staining, immunohistochemistry and HER2 gene amplification were evaluated. In addition, 343 cases of gastric adenocarcinoma diagnosed in the same period were used as the control group to compare the clinicopathological differences between them. Results: The 12 cases of GAED included 10 males and 2 females, aged 59-75 years (median 66.5 years). The main clinical manifestations were abdominal pain, melena with hematemesis; nine tumors were ulcerative and three were protuberant. The tumor diameter ranged from 1.5 to 9.5 cm (median 6.0 cm). Histologically, the tumor cells were arranged in tubular, papillary, cribriform, or adenoid structures. The cells were cuboidal to columnar, with relatively distinct cell boundaries and abundant clear or slightly eosinophilic cytoplasm. Immunohistochemically, tumor cells were positive for SALL4 (12/12), glypican-3 (9/12), AFP (5/12), CDX2 (8/12), CD10 (3/12), p53 mutated (10/12), HER2 (2/12, 3+), and both cases showed HER2 gene amplification by fluorescence in situ hybridization. Compared with common gastric adenocarcinoma, GAED showed higher rate of vascular invasion and tumor progression (P<0.05), but there were no significant differences in age, sex, degree of differentiation, nerve invasion, lymph node metastasis, pT stage, pN stage and pM stage (P>0.05). Conclusions: GAED is a rare type of gastric adenocarcinoma. Pathologically, GAED has both embryonal and intestinal phenotypes. In terms of biological behavior, it is more invasive. GAED needs to be distinguished from common gastric adenocarcinoma in clinical diagnosis.

[Primary extraskeletal osteosarcoma: a clinicopathological study of ten cases].

Objective: To investigate the clinicopathologic features, differential diagnosis, immunohistochemical profiles and molecular characteristics of primary extraskeletal osteosarcoma (ESOS). Methods: Ten cases of ESOS diagnosed and treated in Fujian Provincial Hospital, Fuzhou, China from January 2003 to January 2019 were collected and subjected to immunohistochemical staining and molecular analyses. The patients were followed up by telephone interview. Relative literature was also reviewed to assess the characteristics of this tumor. Results: The ten cases occurred in 3 women and 7 men, aged from 36 to 85 years (median, 60 years). The sizes of these tumors ranged from 5.5 to 17.5 cm (median, 11.0 cm). Histologically, at low magnification, the tumors were nodular, leafy and lobulated. They were composed of spindle cells, neoplastic osteoid cells, and cartilage tissues, with unequally-proportional mixture of these components. The three components intermingled with each other. Immunohistochemistry profiling showed that the tumor cells were positive for SATB2 (9/9), while α-SMA (4/10) and EMA (1/10) stains were focally positive. Ki-67 proliferation index was 10%‒50%. Desmin, CD68, S-100 protein, SOX10, HMB45, CD117, DOG1, CD34, CKpan, GATA3 and PAX8 stains were negative. MDM2/CDK4 gene amplification signals were not detected in the 6 cases (0/6), which were subjected to the FISH. The SSX18 break-apart signal and the C-KIT and PDGFR-α mutations were not detected (0/5 and 0/3, respectively). Conclusions: Primary ESOS is an extra-osseous osteogenic tumor. The diagnosis is mainly dependent on clinical, radiological and pathological characteristics. Immunohistochemistry and molecular profiling are helpful for making the correct diagnosis.

[Pulmonary malignant perivascular epithelioid cell tumor mixed with lung adenocarcinoma components: a case report and literature review].

Objective: To analyze the pathogenesis, clinical manifestations, diagnosis, treatment and prognosis of pulmonary malignant perivascular epithelioid cell tumor (PEComa) with adenocarcinoma. Methods: In August 2020, the Department of Pathology, Dongguan People's Hospital of Southern Medical University, diagnosed a case of pulmonary malignant PEComa mixed with adenocarcinoma. The clinical data, pathological diagnosis, treatment plan and prognosis of the patient were analyzed, and the literature was reviewed. Firstly, "malignant perivascular epithelioid cell tumor"+" Pulmonary "+"adenocarcinoma" was used to search CNKI and Wanfang Medical Database, but no relevant reports were found. Then, we changed the search term as "pulmonary malignant perivascular epithelioid cell tumor", and search for PubMed, Embase, Web of Science and Cochrane by combining the subject terms with "pulmonary malignant perivascular epithelioid cell tumor" and "PEComa" as subtopics. The language was Chinese or English and the search deadline was November 2020. Results: The patient, a 46-year-old male, was admitted to the hospital on August 20, 2020, due to "repeated cough and chest pain for more than 10 days, accompanied by rapid weight loss". Serology detected increased expression of lung non-small cell lung cancer related antigens. PET-CT showed a large mass of soft tissue density in the left thoracic cavity with an SUV value of 22.8. The postoperative pathological diagnosis was malignant PEComa mixed with adenocarcinoma and the lymph nodes were metastasized. Due to the detection of EGFR sensitive mutation, postoperative chemotherapy and targeted therapy were administered, and the current state was stable. A total of 12 cases of pulmonary malignant PEComa were retrieved in the literature, which were common in middle-aged and elderly people. They usually presented with cough or chest tightness. Chest CT mostly showed round masses with clear boundaries, and 8 cases had metastasis to mediastinal lymph nodes and other organs. Conclusions: Pulmonary malignant PEComa is rare. It is the first report of the same mass with lung primary adenocarcinoma. The tumor progresses rapidly. Complete surgical resection of the lesion and lymph node dissection are more appropriate treatment strategies, supplemented by postoperative chemotherapy and targeted therapy. For cases diagnosed as pulmonary PEComa, long term follow-up should be performed, even if the pathological diagnosis is benign.

[Prevalence of deep venous thrombosis in chronic refractory wounds and its influencing factors].

Objective: To investigate the incidence and risk factors of lower extremities deep venous thrombosis (DVT) in patients with chronic refractory wounds (chronic wounds). Methods: A retrospective analysis of 722 cases of chronic wounds admitted to the First People's Hospital of Zhengzhou from January 1, 2015 to December 31, 2018 was carried out, and clinical data such as gender, age, wound involves the lower extremities, wound type, duration of wound, D-dimer level and complicated diabetes, hypertension, coronary heart disease, cerebral infarction, pneumonia and sepsis/septic shock were collected. The patients were divided into DVT group and non-DVT group according to the color ultrasound test. Multivariate binary logistic regression analysis was used to screen the independent risk factors of DVT in patients with chronic wounds. Results: There were 55 (7.6%) patients in DVT group, of which 44(80.0%) were diagnosed as chronic DVT by conventional lower extremities venous color ultrasound screening at admission, and the remaining 11(20.0%) were newly diagnosed during hospitalization. There were no significant differences in gender, wound involves the lower extremities, duration of wound, complicated diabetes and hypertension between DVT group and non-DVT group (all P>0.05); and the differences were statistically significant in age, wound type, D-dimer level, complicated coronary heart disease, cerebral infarction, pneumonia and sepsis/septic shock (all P<0.05). Multivariate binary logistic regression analysis showed age [OR=2.260 (95%CI: 1.584-3.224)], D-dimer level [OR=14.201 (95%CI: 6.101-33.055)], complicated coronary heart disease [OR=2.731 (95%CI: 1.210-6.162)] and sepsis/septic shock [OR=3.170 (95%CI: 1.115-9.016)] were independent risk factors for DVT (all P<0.05). Conclusion: Chronic wounds patients have a higher incidence of DVT, most of which are chronic DVT, and age, D-dimer level, complicated coronary heart disease and sepsis/septic shock are independent risk factors for DVT in chronic wounds.

[Malignant gastrointestinal neuroectodermal tumor: clinicopathological analyses of four cases].

Objective: To investigate the clinicopathological features, diagnosis, differential diagnosis, and molecular alterations of malignant gastrointestinal neuroectodermal tumor (MGNET). Methods: Four cases of MGNET were collected at Fujian Provincial Hospital, from July 2013 to January 2019. H&E and immunohistochemical staining were retrospectively evaluated, together with genetic mutation analysis of EWSR1. The relevant literature was systematically reviewed. Results: There were two male and two female patients, with an age range of 34-81 (median 57) years. Tumor sizes ranged from 5-9 (median 6.8) cm. Microscopy showed diffuse and flaky growth of tumor cells, some of which were small and round. The tumor cells were arranged in solid, flaky, nested or pseudoadenoid patterns. The tumor cells were epithelioid, oval, short spindled, or small, with round or oval nuclei. The cytoplasm was eosinophilic or clear. Osteoclast-like multinucleated giant cells were scattered focally. Mitosis was about (2-10)/10 HPF. Immunohistochemically, the tumor cells were positive for S-100 protein (4/4), SOX10 (4/4), Syn (2/4), INI1 (4/4), H3K27Me3 (4/4) and vimentin (4/4). Ki-67 index was 15%-90%. Gene mutation detection confirmed EWSR1 mutation in all four cases, and C-KIT/PDGFRα genes were not mutated in two cases. Conclusions: MGNET is a rare high grade malignant soft tissue tumor. The diagnosis is based on clinicopathological, immunophenotypic, and molecular pathology features. The primary treatment for MGNET is complete surgical excision and chemotherapy; the prognosis is poor.

[Clinicopathological characteristics of indeterminate dendritic cell tumor of four cases].

Objective: To investigate the clinicopathologic features, diagnosis, differential diagnosis and molecular pathological characteristics of indeterminate dendritic cell tumor (IDCT). Methods: Four cases of IDCT were collected at Peking Union Medical College Hospital (3 cases) and Fujian Provincial Hospital (1 case). The 4 cases were analyzed, with focus on morphology, immunohistochemistry and BRAF V600E detection. Related literature was reviewed to reveal the characteristics of this tumor. Results: There were 2 males and 2 females aged 30-52 years (mean=40 years). Histopathological characteristics of the tumor cells were round, polygonal. The nuclei were round, with rich eosinophils cytoplasm. The tumor cells arranged in diffuse, sheet, whorl, and fascicle patterns. Mitosis was variable [generally(1-3)/10 HPF] and nucleoli were obvious. Lymphocytes, plasma cells and other infiltrates could be seen in the stroma. Immunohistochemically, tumor cells were positive for S-100 (4/4), CD1a (4/4), CD68 (4/4) and cyclin D1 (3/3), while CD207/Langerin, CKpan, CD21, HMB45, ALK and actin were negative. Ki-67 index was 5%-30%. Gene detection showed BRAF V600E mutations were not present in any of the four cases. Conclusions: IDCT is a rare type of dendritic cell tumor. There are no specific morphology characteristics. The diagnosis depends on clinical, histopathological and immunophenotype. Thus, electron microscopy and molecular testing are helpful if necessary.

[Histopathological and molecular characteristics of metaplastic thymomas: report of five cases].

Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular genetic characteristics and prognosis of the metaplastic thymoma (MT). Methods: The clinicopathological and follow-up data of five MT cases were collected at Fujian Provincial Hospital from 2008 to 2019. Immunohistochemical staining and MAML2 gene detection were performed, and the relevant literature was reviewed. Results: There were 2 males and 3 females, aged 36-64 years (mean age 52 years). The tumors ranged 3.2-7.3 cm in the greatest diameter (average 5.1 cm).Microscopically, the tumor showed a biphasic pattern with epithelial cells merging gradually with the spindle cell component. The two areas transited to each other or had obvious boundary. Both components showed mild atypia. No mitosis was observed in either area, and a small number of lymphocytes were observed in the stroma. Immunohistochemical staining showed that epithelioid cells were positive for CKpan, p63 and E-cadherin. Spindle cells were positive for vimentin and EMA, while the Ki-67 index was less than 5%, and lymphocytes were negative for TdT. MAML2 gene apart signal was detected in two of the cases (2/4) that were tested by FISH. Conclusions: MT is a low-grade malignant epithelioid thymic tumor. Its diagnosis and differential diagnosis are dependent on the morphological characteristics, immunohistochemical staining and MAML2 gene detection. The primary treatment option is surgical resection, with an overall good prognosis.

[Paraganglioma of urinary bladder: a clinicopathological features analysis of 23 cases].

Objective: To investigate the clinicopathological features, diagnosis, differential diagnosis and immunohistochemical (IHC) characteristics of paraganglioma of urinary bladder (PUB). Methods: The clinical and pathological data of 23 cases of PUB were collected at the Second Affiliated Hospital of Fujian Medical University (7 cases); Fujian Provincial Hospital (8 cases); Fujian Medical University Union Hospital (6 cases); and First Affiliated Hospital of Fujian Medical University (2 cases) from May 2010 to November 2018. IHC staining for CK, GATA3, CD56, Syn, CgA, S-100 protein, HMB45, SDHB, OCT3/4 and Ki-67 was done using EliVision method; and the relevant literature was reviewed. Results: There were 14 women and 9 men, aged ranged from 21 to 73 years (median 51 years). Clinically, patients presented with headache, vertigo, palpitation, hypertensive crisis during micturition, hypertension, blurred vision, gross hematuria and paroxysmal pallor. The tumor sizes ranged from 0.9 to 6 cm (mean2.5 cm). Macroscopically, most tumors were exophytic and well delineated within the lamina propria or muscularis propria. The tumors were firm and nodular and showed grayish-tan cut surface. Histologically,the tumor growth pattern was expansive or showed interpenetrating infiltrative growth within the lamina propria or muscularis propria; the tumor cells were typically arranged in distinctive nests (Zellballen) with organoid arrangement; pseudo-rosette were seen in some cases. The cells were rounded or polygonal and had rich, acidophilic or amphophilic cytoplasm and may contain pigmented granules and vacuoles; the nuclei were central or eccentric, with small nucleoli, although occasionally some nuclei were pleomorphic and hyperchromatic. Spindled sustentacular cells could be seen around the nests of tumor cells in some cases. There were abundant vessels that were fissure-like, hemangioma-like or dilated. By IHC, the tumor cells were positive for GATA3 (2/23), OCT3/4 (2/23), CD56 (22/23), Syn (23/23), CgA (22/23), S-100 (sustentacular cell, 23/23) and SDHB (23/23); and negative for CK and HMB45; Ki-67 index was 1%-5%. At follow-up, there was no recurrence or metastasis in 18 cases. Conclusions: The diagnosis of PUB relies on the morphologic and IHC features; but there may be histomorphologic heterogeneity. The most important differential diagnosis is invasive urothelial carcinoma. The tumor cells may show aberrant cytoplasmic expression of OCT3/4; there is no clear correlation between SDHB and OCT3/4 expression in the group.

[Clinicopathological and molecular features of Erdheim-Chester disease accompanied with Langerhans cell histiocytosis].

Objective: To investigate the clinicpathological and molecular features of Erdheim-Chester disease (ECD) as well langerhans cell histiocytosis (LCH). Methods: The clinical, histopathological, molecular findings, immunophenotype, treatment and prognosis in 4 cases of ECD combined LCH were evaluated from February 2015 to September 2018 with review of the relevant literature. Results: 2 cases were male, and 2 were female, aged from 7-55 years. Microscopically, there were two different areas, in the first area, the lesions were composed of foamy histiocytes, spindle-shaped fibroblasts, scattered multinucleated giant cells. Lymphocytes, plasma cells, and giant cells were also found. In the other, the lesions were composed of histiocytes with obvious nuclear groove, associated with a variable number of eosinophils, lymphocytes and plasma cells. Immunephenotype, In the second area, histiocytes were positive for CD1a (4/4), S-100 (4/4),CD207/Langerin (4/4), cyclin D1(4/4), and in the two different area, the histiocytes were positive for CD68, CD163, Braf. Ki-67 positive index 1%-10% BRAF V600E gene mutation was detected in three cases. Conclusion: ECD combined LCH was a very rare histiocytosis tumor and its correct diagnosis relies on histopathologic features, immunohistochemical staining, and BRAF V600E gene detection.

Targeted methylation sequencing of plasma cell-free DNA for cancer detection and classification.

Background: Targeted methylation sequencing of plasma cell-free DNA (cfDNA) has a potential to expand liquid biopsies to patients with tumors without detectable oncogenic alterations, which can be potentially useful in early diagnosis. Patients and methods: We developed a comprehensive methylation sequencing assay targeting 9223 CpG sites consistently hypermethylated according to The Cancer Genome Atlas. Next, we carried out a clinical validation of our method using plasma cfDNA samples from 78 patients with advanced colorectal cancer, non-small-cell lung cancer (NSCLC), breast cancer or melanoma and compared results with patients' outcomes. Results: Median methylation scores in plasma cfDNA samples from patients on therapy were lower than from patients off therapy (4.74 versus 85.29; P = 0.001). Of 68 plasma samples from patients off therapy, methylation scores detected the presence of cancer in 57 (83.8%), and methylation-based signatures accurately classified the underlying cancer type in 45 (78.9%) of these. Methylation scores were most accurate in detecting colorectal cancer (96.3%), followed by breast cancer (91.7%), melanoma (81.8%) and NSCLC (61.1%), and most accurate in classifying the underlying cancer type in colorectal cancer (88.5%), followed by NSCLC (81.8%), breast cancer (72.7%) and melanoma (55.6%). Low methylation scores versus high were associated with longer survival (10.4 versus 4.4 months, P < 0.001) and longer time-to-treatment failure (2.8 versus 1.6 months, P = 0.016). Conclusions: Comprehensive targeted methylation sequencing of 9223 CpG sites in plasma cfDNA from patients with common advanced cancers detects the presence of cancer and underlying cancer type with high accuracy. Methylation scores in plasma cfDNA correspond with treatment outcomes.

Wolbachia-induced apoptosis associated with increased fecundity in Laodelphax striatellus (Hemiptera: Delphacidae).

Wolbachia influence the fitness of their invertebrate hosts. They have effects on reproductive incompatibility and egg production. Although the former are well characterized, the mechanistic basis of the latter is unclear. Here, we investigate whether apoptosis, which has been implicated in fecundity in model insects, influences the interaction between fecundity and Wolbachia in the planthopper Laodelphax striatellus. Wolbachia-infected females produced about 30% more eggs than uninfected females. We used the terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling staining to visualize apoptosis. Microscopic observations indicated that the Wolbachia strain wStri increased the number of ovarioles that contained apoptotic nurse cells in both young and aged adult females. The frequency of apoptosis was much higher in the infected females. The increased fecundity appeared to be a result of apoptosis of nurse cells, which provide nutrients to the growing oocytes. In addition, cell apoptosis inhibition by caspase messenger RNA interference in Wolbachia-infected L. striatellus markedly decreased egg numbers. Together, these data suggest that wStri might enhance fecundity by increasing the number of apoptotic cells in the ovaries in a caspase-dependent manner. Our findings establish a link between Wolbachia-induced apoptosis and egg production effects mediated by Wolbachia, although the way in which the endosymbiont influences caspase levels remains to be determined.