Paraganglioma (PGL) is a rare neuroendocrine tumor that causes endocrine hypertension. All paragangliomas had metastatic potential. The 5-year survival rate of patients with metastatic paraganglioma is less than 50%, and the treatment is a big problem. Metastatic PGL has a high specific uptake of iodine [ 131I]-meta-iodobenzylguanidine ( 131I-MIBG), so the treatment is effective, well tolerated, and has few adverse reactions. However, there is a lack of relevant detailed clinical diagnosis and treatment data in China. This article reports the diagnosis and treatment of a case of multi-site metastatic paraganglioma with multiple courses of 131I-MIBG, and discusses the efficacy, safety and tolerance of the treatment for clinical reference.

MAGED4B belongs to the melanoma-associated antigen family; originally found in melanoma, it is expressed in various types of cancer, and is especially enriched in glioblastoma. However, the functional role and molecular mechanisms of MAGED4B in glioma are still unclear. In this study, we found that the MAGED4B level was higher in glioma tissue than that in non-cancer tissue, and the level was positively correlated with glioma grade, tumor diameter, Ki-67 level, and patient age. The patients with higher levels had a worse prognosis than those with lower MAGED4B levels. In glioma cells, MAGED4B overexpression promoted proliferation, invasion, and migration, as well as decreasing apoptosis and the chemosensitivity to cisplatin and temozolomide. On the contrary, MAGED4B knockdown in glioma cells inhibited proliferation, invasion, and migration, as well as increasing apoptosis and the chemosensitivity to cisplatin and temozolomide. MAGED4B knockdown also inhibited the growth of gliomas implanted into the rat brain. The interaction between MAGED4B and tripartite motif-containing 27 (TRIM27) in glioma cells was detected by co-immunoprecipitation assay, which showed that MAGED4B was co-localized with TRIM27. In addition, MAGED4B overexpression down-regulated the TRIM27 protein level, and this was blocked by carbobenzoxyl-L-leucyl-L-leucyl-L-leucine (MG132), an inhibitor of the proteasome. On the contrary, MAGED4B knockdown up-regulated the TRIM27 level. Furthermore, MAGED4B overexpression increased TRIM27 ubiquitination in the presence of MG132. Accordingly, MAGED4B down-regulated the protein levels of genes downstream of ubiquitin-specific protease 7 (USP7) involved in the tumor necrosis factor-alpha (TNF-α)-induced apoptotic pathway. These findings indicate that MAGED4B promotes glioma growth via a TRIM27/USP7/receptor-interacting serine/threonine-protein kinase 1 (RIP1)-dependent TNF-α-induced apoptotic pathway, which suggests that MAGED4B is a potential target for glioma diagnosis and treatment.
Humans ; Tumor Necrosis Factor-alpha ; DNA-Binding Proteins/metabolism* ; Ubiquitin-Specific Peptidase 7 ; Cisplatin ; Temozolomide ; Transcription Factors ; Glioma ; Cell Proliferation ; Melanoma ; Cell Line, Tumor ; Apoptosis ; Nuclear Proteins/genetics*

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl₄. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6C^high macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl₄-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl₄-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Sorafenib/therapeutic use* ; Liver Neoplasms/metabolism* ; Glutamate-Ammonia Ligase/metabolism* ; Hepatectomy ; Retrospective Studies ; Prognosis ; Neoplasm Recurrence, Local/surgery*

Pheochromocytoma/paraganglioma is an adrenal tumor that secrets catecholamines and is extremely rare in pregnant women. Its clinical presentation is lack of specificity, and the combination of low prevalence and nonspecific clinical presentation makes diagnosis and treatment difficult. In this study, the clinical data and prognosis of 5 pregnant patients with pheochromocytoma/paraganglioma were analyzed. It was found that hypertension first occurred in 4 patients during pregnancy, and the clinical manifestations of each case were different. Surgical treatment is the first choice in the treatment, patients who cannot operate can choose radionuclide therapy, chemotherapy and targeted therapy. Through follow-up, they all showed recurrence and metastasis at different times. Among them, the patients who continued to be pregnant to the middle and late stages of surgical treatment progressed rapidly, and there were multiple bone metastases throughout the body in a short period of time, and two cases died in a short period of time. Therefore, effective diagnosis, individualized treatment and lifelong follow-up are particularly important.

Objective: To discuss the effects of acupuncture plus Tuina (Chinese therapeutic massage) in intervening the mental development, motor function, cerebral hemodynamics, and muscle tone in kids with spastic cerebral palsy (CP). Methods: A retrospective analysis was conducted on 87 kids with spastic CP. They were divided into a control group and an observation group based on their original treatment plan. Kids in the control group received symptomatic treatment, motor development therapy, and Tuina treatment. The observation group was additionally given acupuncture treatment. One month was taken as a treatment course. After six courses, the efficacy, change in muscle tone, mental development, gross motor function, fine motor function, and the systolic velocity (Vs), mean velocity (Vm), and pulsatility index (PI) of the anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) were compared between the two groups. Results: After treatment, the muscle tone score dropped in both groups (P<0.05) and was significantly lower in the observation group than in the control group (P<0.05). The observation group achieved more significant efficacy than the control group (P<0.05). After the intervention, the mental development index (MDI), psychomotor development index (PDI), gross motor function measure (GMFM) score, and fine motor function measure (FMFM) score all increased in both groups (P<0.05) and were notably higher in the observation group than in the control group (P<0.05). After treatment, the Vs and Vm of the ACA, MCA, and PCA were markedly higher in the observation group than in the control group (P<0.05), and the observation group was significantly lower than the control group comparing the PI of the ACA, MCA, and PCA (P<0.05). Conclusion: Based on the symptomatic treatment and motor development therapy, Tuina and acupuncture treatment can effectively treat spastic CP children, manifesting as reducing muscle tone, boosting mental development, and improving motor function and cerebral hemodynamics.

Objective:To investigate the current situation of occupational hazards in automobile manufacturing enterprises in Shandong Province.Methods:From February to May 2019, the convenience sampling method was adopted to conduct on-site occupational health surveys with 20 automobile manufacturing enterprises in Shandong Province as the survey subjects, to detect the occupational hazard factors in the workplaces and individual exposure levels, and to analyze the occupational health check results of operators.Results:There were 13 small-sized, 4 medium-sized and 3 large-sized enterprises among the 20 automobile manufacturing enterprises. The detection results of benzene and toluene in the workplaces met the occupational exposure limits, and the detection results of welding fumes, manganese and its compounds, and xylene exceed the occupational exposure limits. The maximum short-term exposure concentration ( CSTE) of welding fume in the air of workplaces was 24.23 mg/m 3, and the over-standard rate was 11.0% (16/146) . The maximum time-weighted average concentration ( CTWA) of welding fume of operators is 10.60 mg/m 3, and the over-standard rate was 11.0% (8/73) . The maximum CSTE of manganese and its compounds in the air of workplaces was 0.879 mg/m 3, and the of manganese and its compounds of operators was 0.175 mg/m 3, and the over-standard rate was 5.7% (4/70) . The maximum xylene CSTE in the air of workplaces was 230.00 mg/m 3, and the over-standard rate was 3.9% (2/51) . The maximum xylene CTWA of operators was 70.40 mg/m 3, the over-standard rate was 3.6% (1/28) . Among the 4775 workers exposed to occupational hazards, 38 (0.80%) were suspected of electric welder's pneumoconiosis, 27 (0.57%) were suspected of manganese poisoning and 31 (0.65%) were suspected of chronic low-concentration benzene and benzene series poisoning. The detection rates of suspected occupational diseases among workers in small and medium-sized enterprises were relatively high, 2.86% (30/1048) and 4.51% (51/1132) respectively. There was a statistically significant difference in the detection rates of suspected occupational diseases among the operators of different scale automobile manufacturers ( P<0.05) . Conclusion:The exposure levels of electric welding fumes, manganese and its compounds in welding jobs and xylene exposure levels in spray painting jobsin Shandong Province's automobile manufacturing enterprises are more serious. The supervision and management of occupational hygiene should be strengthened, the working environment should be improved, and the health of welding and painting workers should be protected.

Objective:To investigate the current situation of occupational hazards in automobile manufacturing enterprises in Shandong Province.Methods:From February to May 2019, the convenience sampling method was adopted to conduct on-site occupational health surveys with 20 automobile manufacturing enterprises in Shandong Province as the survey subjects, to detect the occupational hazard factors in the workplaces and individual exposure levels, and to analyze the occupational health check results of operators.Results:There were 13 small-sized, 4 medium-sized and 3 large-sized enterprises among the 20 automobile manufacturing enterprises. The detection results of benzene and toluene in the workplaces met the occupational exposure limits, and the detection results of welding fumes, manganese and its compounds, and xylene exceed the occupational exposure limits. The maximum short-term exposure concentration ( CSTE) of welding fume in the air of workplaces was 24.23 mg/m 3, and the over-standard rate was 11.0% (16/146) . The maximum time-weighted average concentration ( CTWA) of welding fume of operators is 10.60 mg/m 3, and the over-standard rate was 11.0% (8/73) . The maximum CSTE of manganese and its compounds in the air of workplaces was 0.879 mg/m 3, and the of manganese and its compounds of operators was 0.175 mg/m 3, and the over-standard rate was 5.7% (4/70) . The maximum xylene CSTE in the air of workplaces was 230.00 mg/m 3, and the over-standard rate was 3.9% (2/51) . The maximum xylene CTWA of operators was 70.40 mg/m 3, the over-standard rate was 3.6% (1/28) . Among the 4775 workers exposed to occupational hazards, 38 (0.80%) were suspected of electric welder's pneumoconiosis, 27 (0.57%) were suspected of manganese poisoning and 31 (0.65%) were suspected of chronic low-concentration benzene and benzene series poisoning. The detection rates of suspected occupational diseases among workers in small and medium-sized enterprises were relatively high, 2.86% (30/1048) and 4.51% (51/1132) respectively. There was a statistically significant difference in the detection rates of suspected occupational diseases among the operators of different scale automobile manufacturers ( P<0.05) . Conclusion:The exposure levels of electric welding fumes, manganese and its compounds in welding jobs and xylene exposure levels in spray painting jobsin Shandong Province's automobile manufacturing enterprises are more serious. The supervision and management of occupational hygiene should be strengthened, the working environment should be improved, and the health of welding and painting workers should be protected.

Objective:To investigate the clinicopathological characteristics of the T cell lymphomas with CD20 expression, and to better understand this rare entity.Methods:Two-hundred cases of T-cell lymphoma diagnosed in the Department of Pathology of the Affiliated Hospital of Qingdao University from November 2016 to February 2020 were examined, and 5 cases of CD20-positive T-cell lymphomas were identified and included. Combined with clinical data and review of the literature, the clinicopathological characteristics of the disease were analyzed.Results:The five patients were all male, and had an average age of 56 years (range, 47 to 64 years). There were 2 cases of monomorphic epitheliotropic intestinal T-cell lymphoma, 2 cases of mycosis fungoides (1 case was plaque stage and the other was tumor stage) and 1 case of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Immunohistochemistry showed that all 5 cases expressed multiple T cell markers (CD3/CD4/CD5/CD7/CD8) and only one of B cell markers (CD20). Three of the 5 cases were negative for CD20 at the first diagnosis, while CD20 was diffusely positive on the second biopsy from the recurrence or progression of the disease, without expression of CD79a or PAX5. Epstein-Barr encoding region (EBER) in situ hybridization was negative in all 5 cases. T-cell receptor gene analysis showed monoclonal rearrangement of β or/and δ chains;Ig rearrangements were all polyclonal. None of the five patients were treated with rituximab, and 4 patients survived with disease and 1 patient survived without disease at the end of follow-up. Among them, the patient with mycosis fungoides at the cancerous stage has progressed rapidly and had poor quality of life.Conclusions:CD20-positive T-cell lymphoma is extremely rare. Its prognosis is closely related to the type of T-cell lymphoma, clinical stage and initial therapeutic effect. However, the expression of CD20 indicates the recurrence or progression of the disease, and the prognosis is relatively poor. When CD3 expression is absent in T-cell lymphoma, it is easy to be misdiagnosed as B-cell lymphoma. The combination of multiple immunohistochemical antibodies and molecular detection can improve the accuracy of diagnosis.

Objective: To investigate the clinicopathological features of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Methods: Five cases of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract from the Affiliated Hospital of Qingdao University from 2016 to 2019 were retrospectively reviewed. The clinical and pathological parameters were analyzed by combining clinical data and reviewing the available literature of 35 cases (34 cases abroad and 1 case in China). Results: There were 4 males and 1 female with a median age of 47 years (18-66 years). All patients had abdominal pain and constitutional symptoms including diarrhea, emaciation, intermittent mucous stool or oral and epiglottic ulcers. Endoscopic manifestations included multiple punctate congestion, erosion and ulcer at the terminal ileum and colorectum. Two cases had congestion and erosion of antrum and angle of stomach, and the lesions did not fuse and form tumors. Histologically, the lamina propria was expanded by a dense, medium to small lymphocyte infiltration, which was monomorphic, with slightly irregular nuclei without prominent nucleolus or lymphoepithelial lesions. There were admixed small amount of plasma cells and eosinophils. In 4 cases, immunohistochemistry showed the lesional cells were positive for CD3, CD8, TIA1, and negative for CD4, CD56, granzyme B and Ki-67 index was ≤10%. In situ hybridization showed that EBER was negative and clonal TCR gene rearrangement was detected. One consultation case was CD3⁺, CD5^- and Ki-67 index of 10%, although other indicators were not done. All five patients were treated with symptomatic support. In follow-up observation for 2 to 25 months, all patients were alive with the disease. Conclusions Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract is a newly classified monoclonal T-cell proliferative disease, with low incidence, clinical inertia and long-term survival. It has unique clinicopathological features but pathologically it is easily misdiagnosed as inflammatory bowel disease or T-cell lymphoma. Correct diagnosis is of great important clinical significance.