Research Progress on Molecular Mechanism of Lipid-lowering and Anti-inflammatory Effect of Zexietang / 中国实验方剂学杂志

Zexietang is a Chinese herbal compound prescription with a long history， which consists of Rhizoma alismatis and Atractylodes macrocephala. Zexietang comes from "Synopsis of Golden Chamber"， as "there is a drink under the heart， and its people are bitter and dizzy". Zexietang has the effect of removing water from drinking water and invigorating spleen for diuresis. Modern pharmacological studies have shown that its lipid-lowering and anti-inflammatory effects are very significant. It can be used to treat hyperlipidemia， anti-atherosclerosis and non-alcoholic fatty liver disease. With the continuous development of molecular biology， the research on the pharmacological effects of Zexietang， extracts and their monomers has deepened to the molecular level gradually， and the relevant mechanism of action has also been continuously elucidated. In terms of lipid-lowering effect of Zexietang， the levels of cytokines or receptors such as 3-hydroxy-3-methyl glutaryl coenzyme A reductase （HMGCR）， cholesterol 7α-hydroxylase （CYP7A1）， and liver X receptors （LXR） are affected. It is widely involved in adenosine 5'-monophosphate-activated protein kinase （AMPK） and peroxisome proliferators-activated receptors （PPAR） pathways， while Zexietang's anti-inflammatory effect mainly affects inflammatory factors such as interleukins （IL） and tumor necrosis factors （TNF）， and simultaneously nuclear factor κB （NF-κB）， toll-like receptors （TLR） and other cytokines or receptor-related pathways. In order to promote the further research and clinical application of Zexietang and contribute to the development of modernization of traditional Chinese medicine， the studies of the past 15 years on molecular mechanism of the lipid-lowering and anti-inflammatory effect of Zexietang， Alisma and Atractylodes extract as well as their monomer components were reviewed.

Visually Isoattenuating Pancreatic Acinar Cell Carcinoma:Report of One Case / 中国医学科学院学报

Acinar cell carcinoma of pancreas(ACCP)is a rare pancreatic exocrine tumor that accounts for about 1% of pancreatic tumors. The typical imaging manifestations of ACCP are as follows:(1)the tumor is large in volume,partially or completely exophytic;(2)complete or incomplete capsule is visible with thin linear enhancement;(3)CT density and MRI signal:plain CT images reveals that the tumors have similar or slightly hypodense densities relative to the adjacent normal pancreas,the solid part of ACCP has low to intermediate signal intensity on T1WI and intermediate to high signal intensity on T2WI compared with the surrounding normal pancreas;(4)pattern of enhancement:tumors exhibit heterogeneous enhancement and it is less than that in the surrounding normal pancreas;(5)fissure-like,swirling necrosis that may be a characteristic change of tumor;(6)pancreatic and biliary duct dilatation is rare;(7)adjacent organs and blood vessels around the pancreas may be invaded;(8)distant metastasis of liver and other parts may be observed;(9)PET-CT shows high FDG uptake. An ACCP patient with atypical imaging manifestations was treated in Peking Union Medical College Hospital from November 2015 to August 2017. The lesion manifested iso-enhancement and many imaging examinations failed to find the tumor. The patient ultimately underwent surgery and diagnosed as ACCP by pathology.

Application of Sigma Management in Quality Control of Blood Cell for Occupational Health Examination / 现代检验医学杂志

Objective To evaluate the performance of the main indicators in the blood analysis of an occupational health exam ination agency by Sigma verification of performance chart and guide quality improvement.Methods Collected blood testing laboratory internal quality control (IQC) data in October 2016 and 2016 second national external quality assessment (EQA) results of the blood analysis laboratory in the agency.Regarded the accumulated coefficient of variability as the estimation value of imprecision.Used the percentage difference in EQA results as the estimation value of bias (％) of the laboratory.The total allowable error in health industry standard WS/T406-2012 was adopted as the quality specification (％).Sigma verification of performance chart of the main eight projects in the blood analysis were drawn with professional software.Results The sigma value of WBC reached σ≥6 level,as the first-class performance,and the sigma values of HGB in the 4≤σ ＜5 level,test performance was good.The sigma value of Hct,HCV and MCHC all were in the 3≤σ＜4 level,as the critical level,and the sigma values of RBC,platelet and MCH in the 2≤σ＜3 level,as poor performance.Conclusion Sigma verifica tion of performance chart could reflect the level of the laboratory testing performance on different test items of blood count,promote the quality improvement.

Clinicopathological Features of Intraductal Pancreatic Neuroendocrine Tumors / 中国医学科学院学报

Objective To evaluate the clinical and pathologic characteristics of intraductal pancreatic neuroendocrine tumors (PanNETs). Methods Four cases of intraductal PanNETs were studied by light microscopy and immunohistochemistry with the analysis of morphologic features and review of relevant literatures. Results Two female patients and two male patients aged 41- 58 years were enrolled in this study. The chief complaint was abdominal pain in two patients,vomiting in one patient,and jaundice in the last patient. Imaging examination showed intraductal neoplasm with diagnosis as intraductal papillary mucinous neoplasm (IPMN) in case 1; space-occupying lesions were found in the head of pancreas in the other three cases with pancreatic ductal ectasia and distal pancreatic atrophy. Grossly the masses were located in pancreatic main duct and invaded into surrounding pancreatic parachyma. Microscopically the tumors arranged with solid pattern,with some trabecular structures in the last two cases. Small duct and ductules were seen in intraductal PanNETs. The immunohistochemical expression showed that SYN and CgA were positive in neoplastic cells and negative in small duct and ductules.Conclusions Intraductal PanNETs are rare conditions. The clinical symptoms and imaging findings are similar to IPMN or pancreatic carcinoma. The tumors are located within pancreatic duct partly and can invade the pancreatic parenchyma. Microscopically the neuroendocrine tumors mix with small duct and forms ductulo-insular structure,which should be differentiated with mixed ductal endocrine carcinoma. The grade and prognosis are similar to those of classical neuroendocrine tumors.

Intraductal tubulopapillary neoplasm of the pancreas: a clinicopathologic study of 6 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the pathologic features, diagnosis, differential diagnosis and molecular characteristics of intraductal tubulopapillary neoplasm of the pancreas (ITPN).</p><p><b>METHODS</b>The clinical findings, morphologic features, immunophenotype (by EnVision method) and KRAS gene alterations (by reverse transcriptase-polymerase chain reaction) of 6 cases of ITPN encountered during the period from January, 2001 to June, 2010 were analyzed.</p><p><b>RESULTS</b>There were altogether 2 males and 4 females. The mean age of the patients was 64 years. Gross examination showed that the tumors were located in large pancreatic ducts and appeared as polypoid nodules with ductal obstruction. Solid tumor nodules associated with adjoining dilated ducts were identified in one case. Histologically, the tumors were characterized by tubulopapillary growth pattern without luminal mucin. The tumor cells showed high-grade nuclear atypia with scanty intracytoplasmic mucin. Intraductal necrotic foci were frequently observed. Immunohistochemical study showed that the tumor cells expressed CK7 and CK19. Focal positivity for MUC5AC was demonstrated. Two cases expressed MUC1. The staining for MUC2 was negative. KRAS gene mutations were identified in 2 cases, with a single-amino-acid substitution in codon 12 (35G > A and 35G > T/34G > A).</p><p><b>CONCLUSIONS</b>ITPN is a newly described pancreatic intraductal neoplasm and different from intraductal papillary mucinous neoplasm. ITPN is characterized by intraductal tubulopapillary growth pattern, severe cytologic atypia and scanty mucin secretion.</p>

Clinicopathologic features and immunophenotypes of CD117-negative gastrointestinal stromal tumor / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the immunophenotype and c-kit or platelet derived growth factor receptor alpha (PDGFRA) gene mutations in CD117-negative gastrointestinal stromal tumors (GISTs).</p><p><b>METHODS</b>Ten cases of GISTs with typical histologic features but no CD117 expression were retrieved from the archival of Department of Pathology, Peking Union Medical College Hospital, China. The cases were further evaluated for the presence of c-kit exons 9, 11, 13 and 17 mutations and PDGFRA exons 12 and 18 mutations. DNA was extracted from the paraffin-embedded tumor tissue. The PCR products were sequenced directly for the mutations. An immunohistochemical study for CD117, CD34, smooth muscle actin, desmin, S-100 protein, WT-1 and DOG-1 was also performed.</p><p><b>RESULTS</b>Eight of the 10 cases had the mutation tests completed. C-kit mutation in exon 9 was detected in only one case. Amongst the 10 cases studied, CD34 was expressed in 9 cases. Smooth muscle actin was focally positive in 2 cases. None of them expressed desmin or S-100 protein. DOG-1 and WT-1 were diffusely positive in 5 and 4 cases, respectively. In addition, DOG1 was diffusely but weakly positive in 1 case and focally expressed in 2 cases. Three cases were focally positive for WT-1.</p><p><b>CONCLUSION</b>Pathologic diagnosis of CD117-negative GISTs can be facilitated with the application of a panel of immunohistochemical markers, including DOG-1 and WT-1.</p>

Colloid carcinoma of pancreas: a clinicopathologic study of 4 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the pathologic features, diagnosis, differential diagnosis and molecular characteristics of colloid carcinoma of the pancreas.</p><p><b>METHODS</b>The clinical findings, morphologic features, immunophenotype and K-ras gene alterations were investigated in 4 cases of pancreatic colloid carcinoma.</p><p><b>RESULTS</b>In the 4 cases of colloid carcinoma of the pancreas, three tumors were located in the head of the pancreas, one was located in the body and tail. The average age was 56.5 years old. The presenting symptom was abdominal pain in 2 cases, increased level of U-GLU in 1 patient, and an accidental finding presented in 1 patient. Grossly, 3 cases were cystic and solid, with mucin in the cyst; 1 case was solid. Microscopically, the colloid carcinoma was characterized by large pools of extracellular mucin, containing neoplastic cells, which were in the pattern of cuboidal, cribriform or irregular clusters, or formed an incomplete lining separating mucin pools from the stroma. Three cases developed from pre-existing pancreatic ductal adenocarcinoma (IPMN), intestinal-type, and 1 from IPMN, pancreatobiliary-type. Immunohistochemical studies showed that MUC2 was positive in 3 cases, and MUC1 in 1 case. K-ras gene mutation was identified in 2 cases, showing a single-amino-acid substitution in codon 12, as Gly12Asp (GGT > GAT) and Gly12Arg (GGT > CGT).</p><p><b>CONCLUSIONS</b>Pancreatic colloid carcinoma is a rare variant of pancreatic ductal adenocarcinoma, which is associated with IPMN and mucinous cystic neoplasms. Positive MUC2 staining and absent MUC1 expression are commonly found, and K-ras gene mutation is occasionally identified in these tumors.</p>

Intraductal papillary mucinous neoplasm of pancreas: a clinicopathologic and immunohistochemical study of 19 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and diagnosis of intraductal papillary mucinous neoplasm (IPMN) of the pancreas.</p><p><b>METHODS</b>Nineteen cases of IPMN encountered during the period from 1999 to 2007 were studied by light microscopy and immunohistochemistry.</p><p><b>RESULTS</b>IPMN occurred more often in males (68%). It affected patients in older age group (mean age = 59) and was located mainly in the head of pancreas (60%). The mean tumor size was 4.2 cm (range = 1 to 8 cm). The clinical presentation was epigastric pain (53%), weight loss (32%), diabetes (21%), pancreatitis (21%) and jaundice (10%). Pancreatectomy was performed in 18 cases. The remaining patient received bypass surgery only. Features of in-situ or invasive malignancy were present in 15 of the 19 cases (78%). Histologically, the tumor consisted of papillary proliferations protruding into and expanding the pancreatic ducts. Invasion into the surrounding pancreatic parenchyma was noted in 12 cases and chronic pancreatitis was present in 16 cases. Follow-up data (4 to 48 months) were available in 13 patients. Apart from 1 patient who died of other disease, all were still alive. Immunohistochemical study showed that p53 was positive in 6 cases, p16 in 5 cases and fascin in 8 cases. The expression of c-erbB-2 was all negative. Ki-67 index ranged from 1% to 80% (mean = 38%).</p><p><b>CONCLUSIONS</b>Malignant changes are not uncommon in IPMN. The prognosis after surgical resection however is better than that of conventional pancreatic adenocarcinoma. The overexpression of p53, p16 and fascin may be related to tumor progression. The possibility of malignant transformation needs to be considered if the Ki-67 index is over 15%. Early recognition by radiologic examination (including ERCP) and pancreatic cytology would be helpful in early diagnosis. Surgical resection represents the mainstay of treatment and long-term post-operative follow up is needed.</p>

Dyshormonogenetic goiter: clinicopathologic study of four cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and differential diagnosis of dyshormonogenetic goiter.</p><p><b>METHODS</b>The clinical features, histopathologic findings and immunohistochemistry of four cases of dyshormonogenetic goiter were reviewed.</p><p><b>RESULTS</b>Amongst the cases of dyshormonogenetic goiter studied, three were females and one male. The age of disease onset ranged from 6 to 12 years and the age at operation ranged from 13 to 28 years. Three patients presented with symptoms of hypothyroidism and one patient had normal thyroid function. On gross examination, the thyroid was multinodular and covered by fibrous capsule. Histologically, three patterns were observed. The predominant pattern was microfollicular/trabecular, with hyperplastic follicular cells associated with scanty colloid material. The second pattern was macrofollicular, the follicular cells were cuboid in shape, with inconspicuous mitotic figures. The third pattern was microcystic, with papillary component frequently seen. No normal intervening thyroid parenchyma was found. All the patients were on long-term thyroxine replacement therapy after operation and remained well.</p><p><b>CONCLUSIONS</b>Dyshormonogenetic goiter is considered as a form of thyroid hyperplasia due to enzymatic defects in hormone synthesis. The architectural polymorphism and cellular atypia may mimic thyroid neoplasms and cause difficulties in differential diagnosis.</p>