Chemokine is a small protein which plays an impor-tant role in men's physiological function.It has chemotactic ac-tivity and is often secreted by immune cells and glial cells like microglia or astrocytes.Through the effect of chemokine recep-tors on target cells,various immune cells can achieve directional migration and play an important role in the diseases related with immunity and inflammation.CCL2,also known as monocyte chemotactic protein-1 (MCP-1 ),is one member of chemokine CC subfamily (βsubfamily).It can chemokine monocytes, macrophages and T lymphocytes to affect their phagocytosis func-tion and produce antibodies to combat invading microorganisms. In recent years,it has been found that CCL2 plays a key role in the occurrence and development of the problems concerning cen-tral nervous system and immune system as well as cancer, AIDS,leukemia,diabetes and other diseases.This thesis is to give an elaboration on the latest research on CCL2 and the rele-vant diseases.

Purpose To explore the role of cell blocks combined with immunohistochemical examination in the diagnosis and differential diagnosis of malignant pleural effusion,and to explore the role of pleural effusion cell blocks in lung adenocarcinoma molecular pathology examination.Methods 142 cases of malignant pleural effusion based cytology,cell blocks of HE staining and immunohistochemical staining by EnVision twostep were retrospectively analysed,the tumor classification was made through analyzing the characteristics of the cells combined with antibody expression.The detection of epidermal growth factor receptor (EGFR) gene mutation of 40 cases of lung adenocarcinoma diagnosed after immunohistochemical staining were used by ARMS-PCR method.Results Among 142 cases of malignant pleural effusion,there were 99 cases caused by lung adenocarcinoma,4 cases of lung small cell carcinoma,3 cases of lung squamous cell carcinoma,13 cases of breast carcinoma,9 cases of ovarian carcinoma,2 cases of gastric carcinoma,1 case of thyroid carcinoma,1 case of endometrial carcinoma,5 cases of mesothelioma,3 cases of lymphoma,1 case of malignant melanoma,1 case of synovial sarcoma.In 40 cases of lung adenocarcinoma pleural effusion cell block,there were 20 cases with EGFR mutations,9 cases of 19del mutations and 11 cases L858R mutations.Conclusion The pleural effusion cell blocks combined immunohistochemistry are useful to improve the accuracy of diagnosis of patients with pleural effusion,and helpful for the determination of classification and the primary site of tumor,assessment of prognosis.Pleural dffusion cell block may used to detect EGFR mutations of lung adenocarcinoma,which provide new source of specimen for the gene detection of lung adenocarcinoma.

Objective To determine the expression of macrophage migration inhibitory factor (MIF)in different molecular subtypes of breast cancer and its clinical significance so as to detect the biological markers of different molecular subtypes of breast cancer.Methods We divided 100 breast cancer patients into four molecular subtypes by immunostaining:luminal subtype,HER-2(+)subtype,basal-like (BLs)subtype and normal breast-like (NBLs)subtype,and then compared the expression of MIF in the groups.We analyzed the associations of MIF-positive expression rate with age,menstruation,tumor size,auxiliary lymph node metastasis,histological type and grade,and clinical stage of the breast cancer patients.We also compared MVD level and 5-year overall survival rate between MIF-positive patients and MIF-negative ones.Results The positive expression of MIF was correlated with HER2(+)subtype breast cancer and auxiliary lymph node metastasis (P < 0.05 ).The patients with MIF-positive expression had a significantly higher level of MVD than those with MIF-negative expression (P < 0.05 ). Kaplan-Meier method showed that MIF-positive patients had a poor prognosis than MIF-negative ones (Log-rank=1 9.5 1 6,P = 0.000).Conclusion Breast cancer patients with MIF-positive expression may be mostly of HER2 (+)subtype,and tend to develop auxiliary lymph node metastasis.These patients have a significantly higher level of MVD and poor prognosis than those with MIF-negative expression.

Since Parkin was confirmed by the Japanese scholar to be associated with juvenile Parkinson′s disease, it has come to be the focus of the scholars and a lot of researches have been made on it. Apart from Parkinson′s disease, many other disea-ses have also been proved to be associated with the role of Parkin and its interaction with protein substrates, especially in various kinds of cancer diseases and leukemia. This paper focuses on the latest research about Parkin and its development in tumor diseases and leukemia.

Objective To investigate the mechanism of heat transfer process in sand therapy in Uyghur medicine. Methods A mathematical model was developed to describe the heat transfer process between human body and the sand during sand therapy. Temperature field was numerically simulated and analyzed based on this model. Results Temperature field in both human tissues and sand was calculated. The surface temperature of the sand and skin surface changed significantly at the beginning of the sand therapy, while sand temperature (5 cm deep) almost kept constant. The skin temperature dramatically increased at the beginning of the sand therapy and then slightly dropped. When sand was deeper than 10 cm, the thickness of sand would not influence the temperature field in human tissues during sand therapy. High initial temperature of sand might cause harmful skin burn. Threshold skin burn occurred if initial temperature of sand was higher than 64.6 ℃ and if the therapy lasted more than 30 minutes.Conclusion Temperature fieled in human tissues varies significantly with the initial temperature of sand, thickness of sand, and duration of therapy.

Aim To examine the inhibitory effect of re-combinant cardiac troponin fusion protein composed of subunit I and artificial peptide which was called CIS on tumor growth. Methods The CIS ’ s effect on the growth of human umbilical vein endothelial cells ( HU-VEC) was examined using MTT assay in vitro. Chick chorioallantoic membrane model was applied to study the alteration of angiogenesis treated with purified re-combinant CIS protein. The effect of tumor growth trea-ted with CIS was observed using several in vivo mice xenograft models. Results There was a statistically significant reduction in HUVEC cell proliferative rate when the cells were treated with purified CIS fusion protein, which was also shown in a dose-dependent manner. A decreased amount of new blood vessel for-mation ( angiogenesis) on chick embryo chorioallantoic membranes was observed in recombinant CIS protein treated group compared to the untreated control group. A significant inhibition of tumor growth rate was a-chieved in CIS treated mice compared to CIS untreated control mice in 6 different mouse xenograft models. Conclusions The fusion protein CIS shows the inhibi-tory effect on the tumor growth in our in vivo mouse models, and such inhibition could be mediated by the mechanism of CIS’ s effect on the decrease of HUVEC cell proliferation and further the reduction of angiogen-esis in tumor tissues. This work could provide the foundation for the in-depth investigations on the phar-maceutical application of CIS targeting anti-tumor ther-apy.

OBJECTIVETo correlate morphological features with mutations of epidermal growth factor receptor (EGFR) in lung adenocarcinomas.

METHODSAccording to 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Lung Adenocarcinoma Classification, a total of 72 surgically resected lung adenocarcinomas were collected and classified into different histological subtypes and different cell types (hobnail, columnar and polygonal). EGFR gene mutation was detected with the amplification refractory mutation method provided by the EGFR mutation test kit. The correlation between these subtypes and EGFR mutations were evaluated.

RESULTSMutations of EGFR were detected in 48.6% (35/72) of lung adenocarcinomas; 19del and L858R were major mutational types (88.6%, 31/35). EGFR mutations were associated with female gender, non-smoking status, and well to moderately differentiated tumor histology. EGFR mutation types were not associated with age, smoking index, lymph node metastasis, stage, status of whether have or not have inclusion bodies or psammoma bodies and mitotic level. Correlations were observed between acinar and papillary adenocarcinoma subtypes and EGFR mutations according to the new classification. EGFR mutation was rare in the subtype of solid adenocarcinoma with mucin production and almost never observed in special subtypes (mainly mucinous and colloid adenocarcinoma). In addition, EGFR mutation was associated with the hobnail cell type.

CONCLUSIONLung adenocarcinomas of predominate acinar and papillary histological subtypes with hobnail cell morphology are good predictors for EGFR mutations.

Adenocarcinoma ; genetics ; pathology ; Adenocarcinoma, Mucinous ; genetics ; pathology ; Adenocarcinoma, Papillary ; genetics ; pathology ; Female ; Genes, erbB-1 ; Humans ; Lung Neoplasms ; genetics ; pathology ; Lymphatic Metastasis ; Male ; Mutation ; Receptor, Epidermal Growth Factor ; genetics ; Sex Factors ; Smoking

Objective:To study the role of a novel brain-derived peptide hypoxic-ischemic brain damage associated peptide (HIBDAP) in regulating pyroptosis of oxygen-glucose deprived (OGD) microglia.Methods:The sequence of HIBDAP was coupled with the sequence of cell-penetrating peptide transactivator of transcription (TAT) to form TAT-HIBDAP. Fluorescein isothiocyanate (FITC) labeled TAT-HIBDAP was added to microglia cells and observed under fluorescence microscope. Microglia cells were treated with different concentrations of TAT-HIBDAP (1, 5, 10, 20 μmol/L) and then OGD process. Cell pyroptosis was analyzed using lactate dehydrogenase (LDH) assay. The concentration of TAT-HIBDAP with the most prominent inhibiting effects was determined and selected for subsequent experiments. The pyroptosis morphology of the control group, the OGD group and the HIBDAP group (5 μmol/L TAT-HIBDAP+OGD) was observed using transmission electron microscope. The mRNA and protein expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes were examined using real-time quantitative PCR and Western Blot analysis.Results:Fluorescence microscope showed FITC-labeled TAT-HIBDAP could successfully enter microglia cells. Compared with the OGD group, low concentrations of TAT-HIBDAP (1, 5, 10 μmol/L) could significantly reduce microglia pyroptosis and the concentration of 5 μmol/L showed the most prominent effects. Compared with the control group, OGD group showed typical pyroptosis morphology and HIBDAP group showed significantly improved morphology. The mRNA and protein expression of NLRP3 inflammasomes in the OGD group were significantly higher than the control group and also the HIBDAP group.Conclusions:The novel brain-derived peptide HIBDAP may reduce the expression of NLRP3 inflammasomes and inhibit the pyroptosis of OGD microglia.

Neoplasms of perivascular epithelioid cells (PEComas) are characterized by epithelioid to spindle cells with eosinophilic to clear cytoplasm, an intimate relationship with blood vessels, and coexpression of myoid and melanocytic immunohistochemical markers. While most reported hepatic PEComas, such as angiomyolipoma (AML), behave in a benign fashion, emerging PEComas cases without typical characteristics require further clarification. We report a case of primary hepatic perivascular epithelioid cell tumors-not otherwise specified (HPEComas-NOS) with untypical pathological and immunohistochemical features compared to those of the benign hepatic AML cases. HPEComas-NOS may represent a special type of PEComas classified as having "malignant potential" or at "high risk of aggressive behavior", suggesting the need for further clarification of hepatic PEComas and long-term follow-up of patients with HPEComas-NOS.
Female ; Humans ; Liver Neoplasms ; Middle Aged ; Perivascular Epithelioid Cell Neoplasms

Objective To analyze the heterogeneities of hepatitis B virus ( HBV ) reverse transcriptase domain (RT) gene mutations related to nucleos (t)ide analogues (NAs) resistance.Methods Blood samples from 2765 chronic hepatitis B patients with virological breakthrough or poor drug response treated in Ningbo No .2 Hospital and Ningbo Fourth Hospital from April 2011 to March 2018 were collected . According to the medication status , it was divided into LAM monotherapy group ( n =603 ) , LdT monotherapy group (n=147), ADV monotherapy group (n=68), ETV monotherapy group (n=10) and the sequential or combined drug resistance of NAs group (n=365).The resistance mutation sites and drug resistance patterns (pathways) of each group were analyzed .The SPSS 19.0 software was used to analyze the data.Results Among 2765 serum samples, the NAs-related HBV-RT resistance mutations were detected in 1193 cases with an overall mutation rate of 43.15％.The mutation rate of LAM monoclonal resistance group was 62.62％ (603/963) with 19 mutation types, the most common single point mutation was rtM204I/V (40.30％, 243/603).The mutation rate of LdT monoclonal resistance group was 45.51％(147/323), and there were 3 mutation types, with the single point mutation rtM204I/V being the most common (59.86％, 88/147).The mutation rate of the ADV monoclonal resistance group was 17.80％(68/382), mainly rtA181T single point mutation (64.71％, 44/68).The mutation rate of the ETV monoclonal resistance group was 4.06％(10/246), and the single point mutation of rtT184A/G/S/I/L/F was the most common one (80.00％, 8/10).The mutation rate of the sequential or combination therapy group was 41.91％ (365/871), among which the mutation rate of the LAM/LdT poor response or the resistance with the sequential ADV group was 63.39％(142/224), and the most single mutation point was rtA181V/T ( 35.21％, 50/142 );the mutation rate of LAM/LdT poor response or drug-resistant with combined ADV group was 42.19％ (54/128), and the most common mutation point was rtA181V/T (46.30％, 25/54);the mutation rate of LAM/LdT with poor response or resistance after sequential ETV 1.0 mg was 44.66％(117/262), and the most common mutation point was rtL180M+M204I/V+S202G/I (31.62％, 37/117);the LAM/LdT poor response or the drug-resistant ETV combined with ADV group had a mutation rate of 7.14％(5/70), all of which were multi-site mutations;the mutation rate of poor response to ADV or resistant with sequential ETV 0.5 mg group was 28.14％(47/167), all of which were multi-site mutations.Secondary ( compensation ) sites such as rtV173L, rtL180M, and rtV214A, and single-point mutations such as rtV207I/L/G, rtS213Tand rtN238T, which were not fully defined , were detected.The resistance patterns ( pathways ) of NAs monotherapy were relatively simple , and the resistance patterns ( pathways ) of NAs experienced patients ( sequential or combined treatment group ) were complex and diverse, and multiple resistance patterns (pathways) existed, along with NAs increasing in species.Non-first-line NAs-related resistance patterns ( pathways ) showed an overall downward trend sand ETV-related drug-resistant mutation showed an overall upward trend .Conclusion The NAs-related HBV resistance mutation sites ( patterns ) are complex and diverse , especially multi-site mutations , refractory drug resistance mutations, multidrug resistance mutations and cross-resistance mutations.Therefore, the optimization of antiviral treatment strategies and drug resistance management concepts need to be continuously updated .