Activation of HIF-1α/ACLY signaling axis promotes progression of clear cell renal cell carcinoma with VHL inactivation mutation / 中华病理学杂志

Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl2 and hypoxia (1%O2) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl2 and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.

Perivascular epithelioid cell tumor of the lung: a clinicopathological analysis of eight cases / 中华病理学杂志

Objective: To investigate the clinicopathological features of perivascular epithelioid cell tumor (PEComa) of the lung. Methods: Eight PEComa cases of the lung diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China from July 2008 to December 2021 were collected and subject to immunohistochemical staining, fluorescence in situ hybridization and next generation sequencing. The relevant literature was reviewed and the clinicopathological features were analyzed. Results: There were 5 males and 3 females, aged from 18 to 70 years (mean 39 years). There were 3 cases of the right upper lung, 3 cases of the left lower lung, 1 case of the left upper lung and 1 case of the right middle lung. Seven cases were solitary and 1 case was multifocal (4 lesions). Seven cases were benign while one was malignant. The tumors were all located in the peripheral part of the lung, with a maximum diameter of 0.2-4.0 cm. Grossly, they were oval and well circumscribed. Microscopically, the tumor cells were oval, short spindle-shaped, arranged in solid nests, acinar or hemangiopericytoma-like patterns, with clear or eosinophilic cytoplasm. The stroma was rich in blood vessels with hyalinization. Coagulated necrosis and high-grade nuclei were seen in the malignant case, and calcification was seen in 2 cases. Immunohistochemically, the tumor cells were positive for Melan A (8/8), HMB45 (7/8), CD34 (6/8), TFE3 (4/7), and SMA (3/8). All cases were negative for CKpan and S-100. TFE3 (Xp11.2) gene fusion was examined using the TFE3 break-apart fluorescence in situ hybridization in 5 cases, in which only the malignant case was positive. The next generation sequencing revealed the SFPQ-TFE3 [t(X;1)(p11.2;p34)] fusion. Follow-up of the patients ranged from 12 to 173 months while one patient was lost to the follow-up. The malignant case had tumor metastasis to the brain 4 years after the operation and then received radiotherapy. Other 6 cases had no recurrence and metastasis, and all the 7 patients survived. Conclusions: Most of the PEComas of the lung are benign. When there are malignant morphological features such as necrosis, high-grade nuclei or SFPQ-TFE3 gene fusion, close follow-up seems necessary.

Clinicopathological features of esophageal carcinoma with ductal differentiation of esophageal gland / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics of esophageal carcinoma with gland duct differentiation. Methods: The clinical, morphologic and immunohistochemical (IHC) features of eight cases of esophageal carcinoma with gland duct differentiation diagnosed from 2012 to 2022 at the First Affiliated Hospital of Soochow University were summarized. Results: There were four males and four females, with a mean age of 68.5 (range 59-82) years. Two tumors were located in middle esophagus, five in the lower esophagus, and one in the cardia. The mean diameter was 2.4 cm (range 0.6-4.5 cm). The tumor had a bilayer epithelial structure, including the inner luminal epithelium and the outer basal epithelium. Immunohistochemistry showed that CK7 (8/8) and CK18 (8/8) were positive in the inner epithelium. p40 (8/8), p63 (8/8) and CK5/6 (8/8) were positive in the outer epithelium. SMA, calponin and CD117 were all negative. p53 mutants were found in all eight cases (strong and diffuse positivity in 6/8; complete loss of expression in 2/8). No columnar metaplasia, intestinal metaplasia and ectopic gastric mucosa were observed in the surface squamous epithelium in the cases. The mean follow-up time was 21.5 months (range 5-51 months). Seven patients survived and one patient died 31 months after surgery due to recurrence and liver metastasis. Conclusion: Esophageal carcinoma with esophageal gland duct differentiation is a rare tumor with unique histologic and IHC characteristics.

Effects of Polybrominated Diphenyl Ethers on the Human Body Exposure in E-Waste Dismantling Region / 法医学杂志

Objective To discuss the effects of polybrominated diphenyl ethers （PBDEs） exposure in e-waste dismantling region on the human body and provide data support for the identification of environmental health damage to residents in the e-waste dismantling region. Methods Adults in an e-waste dismantling region （exposed group, 54 participants） and a control region （control group, 58 participants） were selected, questionnaires were carried out and blood and urine samples were collected. Blood PBDEs, blood lipids, blood routine, blood lead, urine cadmium, urine chromium and urine nickel were detected. T-test was utilized to compare the differences of PBDEs between the two groups. Multivariate analysis were utilized to compare the differences between the two groups in blood routine indexes. Linear regression was used to analyze the relationship between PBDEs and blood routine. Results Exposure levels of PBDEs were significantly higher in the exposed group （240.00 ng/g, adjusted mass fraction of blood lipids, thereafter） than in the control group （93.00 ng/g, P<0.05）. There was no statistical significance in the differences in most blood routine indexes of the two groups （ P>0.05）, and their reference values were all within normal ranges. Mean platelet volume, plateletcrit, basophils percentage, absolute value of basophils, and mean corpuscular hemoglobin concentration were higher in the exposed group than in the control group （P<0.05）. Platelet distribution widths were lower in the exposed group than in the control group and below the normal reference range （P<0.05）. Conclusion PBDEs exposure in e-waste dismantling region tend to change platelet morphology, the number of basophils, and mean corpuscular hemoglobin concentration, and may pose potential health hazards to local residents.

Risk assessment of exported risk of novel coronavirus pneumonia from Hubei Province / 中华预防医学杂志

To evaluate the exported risk of novel coronavirus pneumonia (NCP) from Hubei Province and the imported risk in various provinces across China. Data of reported NCP cases and Baidu Migration Indexin all provinces of the country as of February 14, 2020 were collected. The correlation analysis between cumulative number of reported cases and the migration index from Hubei was performed, and the imported risks from Hubei to different provinces across China were further evaluated. A total of 49 970 confirmed cases were reported nationwide, of which 37 884 were in Hubei Province. The average daily migration index from Hubei to other provinces was 312.09, Wuhan and other cities in Hubei were 117.95 and 194.16, respectively. The cumulative NCP cases of provinces was positively correlated with the migration index derived from Hubei province, also in Wuhan and other cities in Hubei, with correlation coefficients of 0.84, 0.84, and 0.81. In linear model, population migration from Hubei Province, Wuhan and other cities in Hubei account for 71.2%, 70.1%, and 66.3% of the variation, respectively. The period of high exported risk from Hubei occurred before January 27, of which the risks before January 23 mainly came from Wuhan, and then mainly from other cities in Hubei. Hunan Province, Henan Province and Guangdong Province ranked the top three in terms of cumulative imported risk (the cumulative risk indices were 58.61, 54.75 and 49.62 respectively). The epidemic in each province was mainly caused by the importation of Hubei Province. Taking measures such as restricting the migration of population in Hubei Province and strengthening quarantine measures for immigrants from Hubei Province may greatly reduce the risk of continued spread of the epidemic.

Spindle cell lipoma/pleomorphic lipoma of soft tissue: a clinicopathologic analysis of 8 cases / 临床与实验病理学杂志

Purpose To investigate the clinicopathological features, the diagnosis and differential diagnosis of spindle cell lipoma/pleomorphic lipoma (SCL/PL). Methods Eight cases of SCL/PL were studied by HE staining and immunohistochemistry. The literature was reviewed. Results Microscopically, the neoplasm consisted of spindle cells, mature adipocytes and thick rope-like collagen bundles in variable proportions with mucinous degeneration. The floret-like multinucleated giant cells were easy to be seen in the pleomorphic lipoma. Immunohistochemical analysis revealed that the tumor cells were positive for CD34 and vimentin. The Ki-67 was approximately 2％. The patients were followed up for 3 ～ 74 months, and no recurrence or metastasis occurred. Conclusion The SCL/PL is a special subtype of benign lipoma, surgery is considered the first choice, and outcome is favorable. The diagnosis and differential diagnosis of SCL/PL are important.

Expression of gC1qR gene in ovarian cancer and its apoptotic mechanism / 临床与实验病理学杂志

Purpose To investigate the expression of globular C1q receptor (gC1qR) in ovarian cancer and to explore its potential molecular mechanism.Methods Retrospective analysis was made on 48 ovarian cancer tissues and ovarian cancer cell line SKOV3.Real time PCR and Western blot analysis were applied to detect the levels of gC1qR mRNA and gC1qR protein expression.The abilities of SKOV3 cells proliferation activity and quantity,migration and apoptosis were respectively assessed by M'TT,transwell assay and flow cytometry.Besides,the intracellular ROS was estimated via the fluorescence of H2DCFDA,the mitochondrial membrane potential was tested using a JC-1 probe,and the intracellular Ca2+ was assessed via Fluo-3/AM.Results The expressions of gC1qR gene was obviously decreased in the group of ovarian cancer tissues when compared with normal ovarian tissues group (2.61 ±0.34 vs 7.32 ± 1.25,0.20 ± 0.02 vs 0.67-± 0.06,P ＜ 0.001).Overexpression of gC1qR gene could result in significant up-regulation of ovarian cancer cell apoptosis and down-regulation in proliferation and migration,and showed significant cell apoptosis morphology.Simultaneously,the intracellular ROS and Ca2+ were obviously increased,and the mitochondrial membrane potential was obviously decreased.Conclusion gC1qR gene may play an important role in the apoptosis of ovarian cancer cells.In this process,gC1qR gene can induce apoptosis of ovarian cancer cells by inducing mitochondrial dysfunction.

An unusual case of Welder's siderosis with local massive fibrosis: a case report / 中华医学杂志(英文版)

Welder's siderosis was traditionally described as "benign pneumoconiosis" because of the absence of associated symptoms, functional impairment or pulmonary fibrosis. Although several authors have reported evidence of fibrosis in the lungs of welders, siderosis with local massive fibrosis has been rarely described. In this paper, we present a case of Welder's siderosis with local massive fibrosis mimicking lung cancer.

Growth and infiltration of human monocytic leukemia cell in nude mice: a model for central nervous system leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To establish a model of human monocytic leukemia with CNS infiltration in BALB/c nude mice.</p><p><b>METHODS</b>BALB/c nu/nu mice pre-treated by splenectomy, cytoxan intraperitoneal injection, and sublethal irradiation (SCI), were transplanted intravenously with 1 x 10(7) of human monocytic leukemic SHI-1 cells. The leukemic cells engrafted in the mice were detected by RT-PCR, histopathological examination, immunohistochemistry and FCM.</p><p><b>RESULTS</b>The survival time of SCI-nu/nu mice was 33-46 d. Paraplegia occurred in some of the mice. 5 weeks after transplantation, SHI-1 cells engrafted in SCI-nu/nu mice, multi-organs were involved and green solid neoplasms were formed in some organs. Histopathological examination found that SHI-1 cells infiltrated in liver, lung, kidney and testis of the mice and vertebral and skull bone marrow was replaced by leukemic cells. Leukemic cell penetrated through the surface of vertebrae, formed neoplasm, and entered the subdural space, but seldom involved the spinal parenchyma. In brain leukemia cells were filled in the subdural space and pia-arachnoid, covered the surface of cerebrum, cerebellum, spread along the virchow-robin space on the surface of pia mater, and eventually invaded the brain parenchyma.</p><p><b>CONCLUSION</b>SHI-1 cells could engrafted in the SCI-nu/nu mice, form an efficient and reproducible experimental model of CNSL and systematic leukemia. This model may be useful for studying the pathogenesis of CNSL.</p>