First Measurement of Discrimination between Helium and Electron Recoils in Liquid Xenon for Low-Mass Dark Matter Searches.

We report the first measurement of discrimination between low-energy helium recoils and electron recoils in liquid xenon. This result is relevant to proposed low-mass dark matter searches which seek to dissolve light target nuclei in the active volume of liquid-xenon time projection chambers. Low-energy helium recoils were produced by degrading α particles from ^{210}Po with a gold foil situated on the cathode of a liquid xenon time-projection chamber. The resulting population of helium recoil events is well separated from electron recoils and is also offset from the expected position of xenon nuclear recoil events.

[Statistical analysis of disability-adjusted life years for stomach and colorectal cancers in Changning District of Shanghai].

Objectives: To analyze the status and temporal changes of disability-adjusted life year (DALY) for stomach and colorectal cancers among registered permanent residents in Changning District of Shanghai Municipality, and provide scientific basis for the prevention and treatment of stomach and colorectal cancers in this district. Methods: Using the cancer registration data of stomach and colorectal cancers from 2002 to 2019, we estimated the indices such as the DALYs, the DALY crude rates, the age-standardized DALY rates, etc. Then we used the Joinpoint regression model to calculate the average annual percent change (AAPC) and annual percent change (APC) to explore the temporal variations in different periods. Results: The DALYs of stomach and colorectal cancers in Changning District from 2002 to 2019 were 55 931 person years and 65 252 person years, respectively. The crude rates of DALY were 512.16/105 and 597.51/105, respectively. We observed a higher disease burden in men than in women, and the peak rate of DALY in stomach cancer was in the 75-79 years age group, while in colorectal cancer the rate was in the 85-years-or-older age group. Joinpoint regression analysis showed that from 2002 to 2019, the age-standardized DALY rate of stomach cancer showed a downward trend (AAPC=-3.86%, P＜0.05), while the trend of colorectal cancer was not statistically significant(AAPC=-0.08%, P＞0.05). However, the trends in the age-standardized DALY rates of colorectal cancer were different between males and females, with males showing an upward trend (AAPC=1.24%, P＜0.05) and females showing a downward trend (AAPC=-1.67%, P＜0.05). Conclusions: The DALY of stomach and colorectal cancers in Changning District of Shanghai showed a decreasing trend. Males and the middle-aged and elderly populations are still the key targets for disease prevention and control in this district.

[Follicular lymphoma with a predominantly diffuse growth pattern with 1p36 deletion: a clinicopathologic analysis of eight cases].

Objective: To investigate the clinical and pathologic features and diagnosis of follicular lymphoma (FL) with a predominantly diffuse growth pattern (DFL) with 1p36 deletion. Methods: Eight cases of DFL with 1p36 deletion diagnosed at Department of Pathology, Beijing Friendship Hospital, Capital Medical University (n=5) and the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital (n=3) from January 2017 to January 2023 were included. Their clinicopathologic features and follow-up data were analyzed. Immunohistochemistry and fluorescence in situ hybridization (FISH) were performed. Results: There were five males and three females, with a median age of 67 years, and inguinal lymphadenopathy was found as the main symptom. Histologically, similar morphologic features were sheared among all cases, with effaced nodal structure and characterized by proliferation of centrocytes in a diffuse pattern, with or without follicular components. The germinal center-related markers such as CD10 and/or bcl-6 were expressed in the tumor cells, and 1p36 deletion but not bcl-2 translocation was appreciable in these cases. Conclusions: DFL with 1p36 deletion is a rare subtype of FL, with some overlaps with other types of FL or indolent B-cell lymphomas in their pathologic features. An accurate diagnosis requires comprehensive considerations based on their clinical, pathologic, immunohistochemical, and molecular features.

[Clinicopathological features of metastatic melanoma in effusion cytology of serosal cavity].

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

[Overexpression of MKRN2 Inhibits the Growth of Ovarian Cancer Cells].

Ovarian cancer has a high mortality with low five-year survival rates. The role of the E3 ligase Makorin ring finger protein 2 (MKRN2) in ovarian cancer is unknown. This study investigated the impact of MKRN2 on the growth of ovarian cancer. MKRN2 expression in ovarian cancer tissue was analyzed by immunohistochemistry. Overexpression of MKRN2 was induced in two ovarian cancer cell lines (SKOV3 and CAOV3) by lentivirus transfection, and expression levels were verified by western blotting. Proliferation and growth were determined by CCK-8 and colony formation assays, while migration was examined using transwell assays and apoptosis by flow cytometry. Xenograft tumors of transfected SKOV3 cells were established in mice, and immunohistochemistry and TUNEL assays measured MKRN2 levels and apoptosis in tumor cells. Reduced levels of MKRN2 in cancerous tissue relative to non-cancerous ovarian tissues. Lentiviral-based MKRN2 overexpression in SKOV3 and CAOV3 cells reduced tumor-associated behavior while inducing apoptosis in vitro. In xenograft tumors, MKRN2 overexpression inhibited ovarian cancer growth and increased apoptosis in vivo. These findings imply the MKRN2 involvement in ovarian carcinogenesis and suggest its potential for treating the disease.

[Short-term efficacy of posterior ankle arthroscopy and tendoscope on ankle-derived flexor hallucis longus ganglion].

Objective: To investigate the short-term clinical efficacy of posterior ankle arthroscopy combined with tendoscope on ankle-origin flexor hallucis longus tendon ganglion. Methods: A follow-up study. Clinical data of 10 patients with hallux ganglion underwent posterior ankle arthroscopy combined with flexor hallucis longus tendoscope in the Tianjin First Central Hospital from January to June 2021 were analyzed retrospectively. There were 5 males and 5 females with a mean age of 42.7 (22-54) years. Disease distribution: 6 patients were on the right side and 4 cases were on the left side. The mean preoperative course of disease was 19.4 months (2-48 months). The patients were followed-up for a mean time of 12.4 months (8-20 months). The relationship between the origin of hallux ganglion and ankle joint was confirmed by ankle MRI and arthrography of ankle joint before the operation. During the operation, the joint capsule was explored, cleared and opened under the posterior ankle arthroscopy firstly, and then part of the tendon sheath of the forefoot was cleared and cut under the flexor hallucis longus tendoscope. American Orthopedic Foot and Ankle Society (AOFAS) forefoot rating scale and visual analogue scale (VAS) of pain were used to evaluate the clinical outcome before and after operation. Postoperative recurrence, perioperative and long-term complications were recorded spontaneously. Results: The cystic fluid signal of all patients could be traced from flexor hallucis longus tendon to the back of ankle joint by MRI before the operation. Intraoperative radiography showed that contrast media flowed from the back of ankle joint to the end of the hallux. The AOFAS score [M(Q1, Q3)] of the patients increased from 70.5(69.0, 87.8) before the operation to 100.0(85.8, 100.0) at the follow-up (P=0.002), and at the mean time, the VAS score decreased from 5.0(3.5, 6.0)to 0.5(0.0, 1.3) (P<0.001). No complications such as infection and recurrence occurred in all patients until the last follow-up. Conclusion: Posterior ankle arthroscopy combined with minimally invasive technique of tendoscope can treat ankle-origin flexor hallucis longus tendon ganglion effectively.

[Clinicopathological and molecular features of metaplastic thymoma].

Objective: To investigate the clinicopathological features, and molecular genetic alterations of metaplastic thymoma (MT). Methods: A total of ten MT cases, diagnosed from 2011 to 2021, were selected from the Department of Pathology of Jinling Hospital, Nanjing University Medical School, Nanjing, China for clinicopathological and immunohistochemical (IHC) examination and clinical follow-up. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and YAP1 C-terminus (YAP1-CT) IHC were performed to detect YAP1::MAML2 fusions. Results: There were four males and six females, ranging in age from 29 to 60 years (mean 50 years, median 54 years). Microscopically, all tumors showed a typical biphasic morphology consisting of epithelial components and gradually or abruptly transitioning spindle cell components. The two components were present in varying proportions in different cases. Immunophenotypically, the epithelial cells were diffusely positive for CKpan, CK5/6 and p63. The spindle cells were diffusely positive for vimentin and focally positive for EMA. TdT was negative in the background lymphocytes. Ki-67 proliferation index was less than 5%. YAP1 and MAML2 break-apart FISH analyses showed that all ten cases had narrow split signals with a distance of nearly 2 signal diameters and may be considered false-negative. Using YAP1::MAML2 fusion FISH assays, abnormal fusion signals were observed in all the ten cases. NGS demonstrated YAP1::MAML2 fusions in all eight cases with adequate nucleic acids; in two cases the fusions were detected by DNA sequencing and in eight cases by RNA sequencing. All ten cases of MT demonstrated loss of YAP1 C-terminal expression in epithelioid cells. Conclusions: MT is a rare and low-grade thymic tumor characterized by a biphasic pattern and YAP1::MAML2 fusions. Break-apart FISH assays may sometimes show false-negative results due to the proximity of YAP1 and MAML2, while YAP1 C-terminal IHC is a highly sensitive and specific marker for MT. Loss of YAP1 C-terminal expression can also be used to screen YAP1::MAML2 fusions for possible MT cases.

[Pulmonary nuclear protein of the testis midline carcinoma:a case report].

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare malignant epithelial tumor that typically occurs in the midline regions such as the head, neck, and mediastinum. This tumor is characterized by rapid development, aggressive growth, and strong invasiveness. Due to its short duration, most patients are diagnosed at advanced stages, often leading to rapid mortality. Although reports on pulmonary NUT carcinoma are uncommon, this article presents a case of pulmonary NUT carcinoma in which the patient repeatedly expectorated bronchial casts and tumor tissue. Additionally, a comprehensive review of relevant literature from recent years is provided to enhance understanding of this disease.

Coherent Lagrangian swirls among submesoscale motions.

The emergence of coherent Lagrangian swirls (CLSs) among submesoscale motions in the ocean is illustrated. This is done by applying recent nonlinear dynamics tools for Lagrangian coherence detection on a surface flow realization produced by a data-assimilative submesoscale-permitting ocean general circulation model simulation of the Gulf of Mexico. Both mesoscale and submesoscale CLSs are extracted. These extractions prove the relevance of coherent Lagrangian eddies detected in satellite-altimetry-based geostrophic flow data for the arguably more realistic ageostrophic multiscale flow.

[Eosinophilic vacuolated tumor of the kidney: clinicopathological and molecular characteristics].

Objective: To study the clinicopathological features, immunophenotype, molecular changes, differential diagnosis and prognosis of eosinophilic vacuolated tumor (EVT) of the kidney. Methods: Four cases were collected retrospectively from 2014 to 2020 at Ningbo Diagnostic Pathology Center. The clinicopathologic features and immunophenotypic profile were studied by light microscopy and immunohistochemistry. Targeted next-generation sequencing (NGS) panel was used to detect cancer-associated mutation. Follow-up and literature review were also performed. Results: Among the 4 patients studied,2 were males and 2 were females. The age of the patients ranged from 44 to 63 years (the mean age: 51 years).Tumor size ranged from 1.5 to 4.2 cm (mean: 2.3 cm). Microscopically, tumors were well-circumscribed, unencapsulated. Thick-walled vessels and entrapped renal tubules were found within or at the periphery of the tumors. The tumors were predominantly composed of nest pattern, and focal tubular pattern. The tumor cells exhibited abundant, eosinophilic, granular cytoplasm and conspicuous, large nucleoli. Prominent intracytoplasmic vacuoles were seen. These cytoplasmic vacuoles varied in size and frequently coalesced into a large space. Loose fibromatous or hyaline stroma was focally noted. Immunohistochemically, the tumor cells in all cases exhibited a CD117+/CK7-phenotype. All cases were positive for CD10 and p504s. MTOR, S6 and cathepsin K were positive in 4 cases. TFE3, CA9, Melan A and HMB45 were negative in all cases. SDHB retained expression. NGS demonstrated MTOR mutations in all cases, and TSC2 mutation in 2 cases. Conclusions: EVT is a rarely oncocytic renal tumor with unique morphology, immunohistochemical phenotype, molecular profile and an indolent behavior. Recognition of the characteristics of this novel but rare entity will allow for better classification of renal tumors.

[Gastric SWI/SNF complex deletion-associated undifferentiated carcinoma with rhabdoid phenotype: a clinicopathological and molecular analysis].

Objective: To investigate the clinicopathological features and molecular genetic characteristics of gastric SWI/SNF complex deletion-associated undifferentiated carcinoma with rhabdoid phenotype. Methods: Six cases of gastric SWI/SNF complex deletion-associated undifferentiated carcinoma with rhabdoid phenotype diagnosed at the Henan Cancer Hospital, Zhengzhou, China from January 2019 to December 2021 were collected. Histological observation, immunohistochemical staining, next-generation sequencing, and detection of mismatch repair (MMR), EBER, and HER2 were performed. The clinicopathological and molecular characteristics were summarized and relevant literatures were reviewed. Results: The 6 patients were all male, aged 48-75 years. Their initial symptoms mainly included abdominal pain, melena, and dysphagia. Endoscopic examinations showed gastric ulcer type masses, and the morphology of H&E were similar: the tumor cells showed diffuse infiltrating growth, no specific structural characteristics, obvious cell atypia, obvious mitoses, and rhabdomyoid cells with unequal proportions of eosinophilic cytoplasm. The immunohistochemistry for CKpan was negative in 3 of the 6 cases, while focal expression of other epithelial markers was found, including EMA (6/6), CK8/18 (4/6), and CK7 (1/6). P53 was diffusely strong positive in 4 cases (4/6), and negative in 1 case (1/6). Ki-67 was highly expressed (positive rate range, 60%-90%). Other related markers such as mesenchymal tumors, lymphoma, melanoma and germ cell tumors were all negative. Detection of the SWI/SNF complex subunit, namely INI1 (SMARCB1), BRG1 (SMARCA4), ARID1A protein detection, was detected in 5 cases with no SMARCA4 expression (5/6), 1 case with no ARID1A expression (1/6), and all cases with SMARCB1 expression (6/6). MMR proteins were examined, and dMMR was found in 1 of the 6 cases. HER2 expression was 0 in 3 cases, 1+ in 1 case, and 2+ in 2 cases, while no amplifications of HER2 gene were detected using FISH. EBER was negative in all 6 cases. Among the 4 cases of surgical radical treatment that were subject to next-generation sequencing, 3 cases showed TP53 mutations; 1 case showed ARID1A gene frame shift mutation, and there were also mutations of ATM, PTEN and other genes. There was 1 case with detected SMARCA4 gene copy number variant, and other gene mutations such as ALK, BRAF, CDKN1B, BRCA2, etc. Conclusions: Gastric SWI/SNF complex deletion-associated undifferentiated carcinoma with rhabdoid phenotype is a poorly differentiated and rare tumor. Detection of SWI/SNF complex related proteins is helpful for its diagnosis. Moreover, gene mutations associated with SWI/SNF complex will become a new indicator for its diagnosis and prognostication, and a potential new target for molecular therapy, which deserves more attention and warrants more research.

[Succinate dehydrogenase-deficient renal cell carcinoma:a clinicopathological, ultrastructural and molecular analysis].

Objective: To investigate the clinicopathological features, immunophenotype, ultrastructure, genetic alterations and prognosis of succinate dehydrogenase-deficient renal cell carcinoma (SDH RCC). Methods: A total of 11 SDH RCCs, diagnosed from 2010 to 2019, were selected from the Department of Pathology of Nanjing Jingling Hospital, Nanjing University School of Medicine for clinicopathologic, immunohistochemical (IHC), ultrastructural investigation and follow-up. The molecular features of seven cases were analyzed by the panel-targeted DNA next generation sequencing (NGS). Results: There were seven males and four females, with ages ranging from 24 to 62 years (mean 41.4 years, median 41 years). Microscopically, SDH RCC was mainly composed of solid and tubular structures with local cystic change. Four cases showed nested or trabecular structure distributed in a loose hypocellular connective tissue or around scar, similar to oncocytoma. The neoplastic cells demonstrated flocculent eosinophilic cytoplasm with typical intracytoplasmic vacuoles. Immunohistochemically, eight cases were negative for SDHB; three cases showed focal and weak expression, whereas normal renal tubular and vascular endothelial cells demonstrated strong cytoplasmic staining. NGS of DNA targeted-panel detected pathogenic mutations of SDHB gene in seven cases (including three cases with equivocal IHC expression of SDHB), without any mutations in other SDH related genes. There were four cases of SDHB missense mutation, one case of frameshift mutation, one case of splicing mutation, and one case of acquired stop codon mutation. Conclusions: SDH RCC is a distinct variant of RCCs with genetic tendency or with hereditary cancer syndrome. NGS is recommended to detect the related gene mutations for a definitive diagnosis. The patients should be closely followed up.

[Anaplastic lymphoma kinase-translocation renal cell carcinoma: clinical and pathological analysis].

Objective: To investigate the clinicopathological features, molecular characteristics, differential diagnosis and prognosis of anaplastic lymphoma kinase (ALK)-translocation renal cell carcinoma. Methods: Two cases of ALK-translocation renal cell carcinoma diagnosed from January 2011 to December 2020 were retrospectively analyzed to characterize their morphological features, immunohistochemical expression and prognosis. Multiple molecular studies including fluorescence in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR), and next-generation sequencing were performed to characterize the genetic alterations. Results: Two patients included one male and one female, with 59 and 57 years old, respectively. Morphologically, case 1 resembled collecting duct carcinoma or renal medullary carcinoma, which demonstrated tubular, microcapsule and reticular structures, with a remarkable myxoid background and lymphocytes infiltration; case 2 resembled Xp11.2 translocation renal cell carcinoma or type 2 papillary renal cell carcinoma, which demonstrated tubular papillary and focal solid structures, with flocculent cytoplasm and many foamy histiocytes, but without myxoid background and lymphocytes infiltration. Immunohistochemistry showed strongly positive expression of ALK. CK7, E-cadherin, vimentin, PAX8 and CD10 showed various degrees of expression, and other antibodies were nonreactive. A variety of molecular assays showed definite ALK gene translocation, with rare VCL-ALK gene fusion (VCL exon and 16-ALK exon 20) in case 1, and EML4-ALK gene fusion (EML4 exon and 2-ALK exon 20) in case 2. Conclusions: ALK-translocation renal cell carcinoma is rare with various morphological features, and is easy to miss and misdiagnose. The characteristic ALK expression and molecular detection of ALK translocation are helpful for diagnosing this type of renal cell carcinoma.

[Papillary renal neoplasm with reverse polarity: a clinicopathological analysis].

Objective: To study the clinical pathological characteristics, immunophenotype, molecular changes and prognosis of the papillary renal neoplasm with reverse polarity (PRNRP). Methods: Nine cases of PRNRP, diagnosed from 2013 to 2019, were retrieved from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine. Histomorphology, immunophenotype and molecular genetics were analyzed with review of the literatures. Results: There were five male and four female patients, aged from 49 to 70 years, with an average age of 60.1 years. During a mean follow-up of 29 months, one patient died for other cause, and the others survived without disease. Microscopically, the tumor cells arranged in papillary structure with a fibrovascular core, the surface of which was covered with a single layer of cuboidal or columnar cells. The most prominent feature was that the tumor nuclei located at the top of the cytoplasm far from the basement membrane, and they were monotonous in size and arranged neatly with no or few nucleoli. Immunohistochemically, all nine cases of PRNRP showed diffuse positive expression of CK7 and E-cadherin, various degrees of P504s expression, and no expression of CD10 and CD117, with a Ki-67 index of 1%-3%. Unlike other papillary renal cell carcinoma, the nine cases of PRNRP all showed characteristic positive expression of GATA3. The fluorescence in situ hybridization assay showed that the majority of PRNRPs (8/9) did not have triploids on chromosomes 7 and 17. The sequencing of the KRAS gene confirmed the presence of a nonsense KRAS mutation in 8 of the 9 cases. Conclusions: PRNRP is a subtype of papillary renal cell carcinoma with characteristic morphological, immunophenotypic and molecular features, and indolent behaviors. More data are needed to define PRNRP as "carcinoma", and a definitive diagnosis of PRNRP is of great significance for proper treatment choice and accurate prognostication.

[Intestinal flora polymorphisms with different lesional stages in an animal model of MAFLD].

Objective: To study the intestinal flora specific differences with different lesional stages of metabolic (disorder) associated fatty liver disease (MAFLD), namely simple steatosis and steatohepatitis, so as to provide a new direction for MAFLD-related intestinal flora transplantation and targeted therapy. Methods: Mice were fed with normal diet, methionine-choline deficient diet (MCD) and a high-fat high-fructose diet (HFHF) for 12 weeks to construct simple steatosis and steatohepatitis models. HE and Sirius scarlet staining was performed to observe the liver pathological changes. The qPCR method was used to evaluate inflammation and liver fibrosis factors. A fully automatic biochemical analyzer was used to detect changes in liver transaminase and blood lipids. 16S rRNA sequencing method was used to observe the intestinal flora differences in the feces of each group of mice. The comparison of means between two groups was performed by t-test, and the comparison of means between multiple groups was performed by one-way analysis of variance. Kruskal-Wallis rank sum test was used for non-normally distributed data. Results: NAFLD scores were determined with pathological sections (HE and Sirius scarlet staining) of mice liver, which showed that the inflammation and liver fibrosis scores of the MCD and HFHF groups were 2.12 ± 0.18 and 1.06 ± 0.24, and 2.22 ± 0.16 and 0.46 ± 0.10, respectively. The degree of liver inflammation and fibrosis was significantly higher in the MCD than the HFHF group (P < 0.001 and P < 0.01). Lipid deposition was higher in the HFHF than the MCD group (P < 0.001), and the scores were 2.36 ± 0.17 and 1.60 ± 0.24 respectively. Simultaneously, the inflammatory [tumor necrosis factor-A (TNF-a), chemokine factor-2 (CXCL-2)] and hepatic fibrosis indicators [vascular smooth muscle actin alpha (a-SMA) and connective tissue growth factor (CTGF)] had confirmed the above-mentioned results at the transcription level. Moreover, the intestinal flora diversity was reduced (P < 0.05) in the MCD group than the HFHF group, and the Simpson and Shannon index were 0.31 ± 0.10 and 0.42 ± 0.05, and 2.03 ± 0.33 and 1.70 ± 0.28, respectively, and the differences were significant between different intestinal flora groups. The levels of Desulfovibrio, Odoribacter, and Roseburia flora were significantly increased in the HFHF than the MCD group, and the levels of Faecalibaculum, Parasutterella, Alipis, Butyricimonas_virosa, Turicibacter_sp, and Romboutsia_ilealis were significantly increased in the MCD than the HFHF group, and the difference was statistically significant (P < 0.05). Conclusion: There are significant differences in intestinal flora diversity between simple steatosis and steatohepatitis models. Therefore, clarifying the difference between the two may provide a new direction for the stage manner treatment of MAFLD.

Estrogen-related receptor participates in regulating glycolysis and influences embryonic development in silkworm Bombyx mori.

Estrogen-related receptors (ERRs) play indispensable roles in development, energy metabolism, and cancers and are metabolic switches in Drosophila. However, the mechanism underlying their metabolic role is unknown in insects. This study analysed the expression profiles of Bombyx mori ERR (BmERR), hexokinase (BmHK), pyruvate kinase (BmPK) and phosphofructokinase (BmPFK) during embryonic development. The expression of BmERR tended to be similar to that of the other genes. We observed a regulatory association between BmERR and glycolytic rate-limiting enzymes by BmERR overexpression, RNA interference (RNAi), and ERR inhibitors in B. mori embryo cells. Subsequently, ERR cis-regulation elements (ERREs) were predicted and identified in the BmPFK promoter. Transfection assays, electrophoretic mobility shift assays and chromatin immunoprecipitation showed that BmERR can bind to one of these elements to regulate the expression of BmPFK. ERREs were also predicted in the BmHK and BmPK promoters. In the eggs, the expression of glycolytic rate-limiting enzyme genes was suppressed when the expression of BmERR was interference by double-stranded BmERR, the glucose levels also was increased. Meanwhile, the development of silkworm embryos was delayed by about 1 day. These results indicate that BmERR can bind to the ERREs of glycolytic gene promoters and regulate the expression of glycolytic genes, ultimately affecting embryonic development in silkworms.

[The role of Wnt/ß-catenin/TCF-4 pathway on biological behavior of renal cell carcinoma and its mechanism].

Objective: To investigate the role of Wnt/ß-catenin/TCF-4 pathway in renal cancer cells and to analyze its possible mechanism. Methods: ß-catenin and TCF-4 were inhibited by siRNA in 786-O cells. The proliferation of transfected cells was detected by CCK8. The cell death of transfected cells was detected by acridine orange -ethidium bromide staining. The expressions of TCF-4, bcl-2, bax and Caspase-3 were detected in transfection group, empty vector group and negative control groups by western blot. Results: The cell proliferation ability of the ß-catenin transfection group was significantly lower than that of the control group (0.443±0.145 vs 0.910±0.721), meanwhile, the cell death rate was significantly increased (16.38±5.32 vs 6.61±1.04), the expression level of Caspase 3 and bax was increased, and the expression of anti-apoptotic protein Bcl-2 was decreased. Decreased TCF-4 led to the same results as inhibition of ß-catenin (all P<0.05). Conclusion: The Wnt/ß-catenin/TCF-4 pathway may play a role in the regulation of proliferation and apoptosis in 786-O renal cancer cells. The mechanism might through regulating of the downstream apoptosis proteins Caspase 3, bax and anti-apoptotic protein Bcl-2.

[Clinicopathological and molecular features of pulmonary enteric adenocarcinoma].

Objective: To investigate the clinicopathological and molecular characteristics of pulmonary enteric adenocarcinoma (PEAC). Methods: The clinical and pathological data of 19 cases of PEAC in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively collected from 2015 to 2019. Immunohistochemistry (IHC) was used to detect the relevant immunophenotypes, amplification refractory mutation system (ARMS) and fluorescence in situ hybridization (FISH) were used to detect the expression of EGFR, KRAS and ALK genes. The patients were followed up, and the relevant literature was reviewed and analyzed. Results: There were 19 cases, including 10 males and 9 females, with a mean age of 58 years (range 33-71 years). Microscopically, the tumors showed moderately to highly differentiated adenoid and/or papillary growth patterns. The tumor cells were highly columnar and sometimes showed pseudostratification. Inflammatory necrosis and scattered nuclear fragmentation were seen in some glandular lumens. IHC showed variable expression of CK7 (19/19), TTF1 (8/19), Napsin A (6/19), villin (17/19), CK20 (16/19) and CDX2 (10/19). Molecular testing showed KRAS mutation in nine cases (9/19), EGFR mutation in one case (1/19), and positive ALK split signal in one case (1/19). In the literature, the reported mutation rate of KRAS in PEAC was much higher than that of EGFR and ALK. All 19 cases underwent surgical resection and 11 cases were subjected to chemotherapy or radiotherapy. Conclusions: PEAC is a rare variant of invasive pulmonary adenocarcinoma, and has similar histological and cytological features to that of colorectal adenocarcinoma. However, detailed medical history, histologic heterogeneity, an IHC combination of CK7(+)/villin(+) and high KRAS mutation rate are the key points of diagnosis. The prognosis needs long-term follow-up and big data statistics.

[Expression of NR4A3/NOR-1 in acinic cell carcinoma of the salivary gland].

Objective: To investigate the diagnostic role of NR4A3/NOR-1 immunohistochemistry in acinic cell carcinoma (AciCC) of the salivary gland. Methods: A total of 142 tumors were collected from 2004 to 2020 at Nanjing Jinling Hospital, including 24 cases of AciCCs, 12 salivary gland secretory carcinomas,14 salivary duct carcinomas,16 adenoid cystic carcinomas,3 basal cell carcinomas,13 mucoepidermoid carcinomas,7 myoepithelial carcinomas,15 pleomorphic adenomas,15 warthin tumor, 8 myoepithelioma,8 basal cell adenomas, and 7 oncocytomas; 28 normal salivary gland tissues and 2 pancreatic AciCC were also included. Results: NR4A3/NOR-1,a nuclear marker,was positive in 91.7% (22/24) of AciCC of the salivary gland,while DOG1,a membranous and cytoplasmic marker, demonstrated a sensitivity of 95.8% (23/24);there was no significant difference in the overall positive rates(P=0.551), but the stain pattern was different. NR4A3/NOR-1 was negative in normal salivary gland tissues and any other types of tumors in the salivary gland; however,DOG1 showed apical staining in the acinar cells in the salivary gland,as well as salivary gland secretory carcinomas,adenoid cystic carcinomas,basal cell carcinomas,mucoepidermoid carcinomas,myoepithelial carcinomas and basal cell adenomas(P<0.001). NR4A3/NOR-1 showed a high sensitivity(91.7%) and specificity(100%) to identify AciCC of the salivary gland,and in combination with DOG1, the sensitivity increased to 100%. Furthermore, NR4A3/NOR-1 were only positive for AciCC arising from salivary glands but not pancreas(0/2)(P=0.018). Conclusion: NR4A3/NOR-1 is a special and sensitive biomarker for AciCC of salivary glands; combined NR4A3/NOR-1 and DOG1 can be an ideal diagnostic immunohistochemical panel for AciCC.

Application of Convolutional Neural Network in Identifying Different Levels of Isokinetic Exercise Efforts.

ABSTRACT: Objective To develop a convolutional neural network （CNN） that can identify isokinetic knee exercises moment of force-time diagrams under different levels of efforts. Methods The 200 healthy young volunteers performed concentric isokinetic right knee flexion-extension reciprocating exercises with maximal effort as well as half the effort at angular velocities of 30°/s and 60°/s twice, respectively, with an interval of 45 min. The moment of force-time diagrams were collected. The 200 subjects were randomly divided into the training set （140 subjects） and the testing set （60 subjects）. The moment of force-time diagrams from subjects in the training set were used to train CNN model, and then the fully trained model was used to predict types of curves from the testing set. Random sampling of subjects along with subsequent development of models were performed 3 times. Results Under the circumstances of isokinetic knee exercises with maximal effort and half the effort, 2 400 moment of force-time diagrams were produced, respectively. Classification accuracy rates of the CNN models after the 3 trainings were 91.11%, 90.49% and 92.08%, respectively, and the average accuracy rate was 91.23%. Conclusion The CNN models developed in this study have a good effect on differentiating isokinetic moment of force-time diagrams of maximal effort exercises from those made with half the effort, which can contribute to identifying levels of efforts exerted by subjects during isokinetic knee exercises.