[Distribution characteristics of tumor infiltrating lymphocytes in EBV-associated lymphoepithelioma-like carcinoma and their clinical significance].

Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20+B cells, CD4+T cells, and FOXP3+Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20+B cells, CD4+T cells and FOXP3+Treg cells in LELC may suggest a better prognosis.

[Relationship between onco-immunological and morphologic characteristics of lymphoepithelioma-like carcinoma and lymphocyte subtypes of peripheral blood].

Objective: To study the relationship between the onco-immunological and morphologic characteristics of lymphoepithelioma-like carcinoma (LELC) and peripheral blood lymphocyte subtypes and its clinical significance. Methods: The pathologic and clinical data of 117 LELC patients who were admitted to the Tumor Hospital of the University of Chinese Academy of Sciences from 2006 to 2018 were collected. The histological classification was based on previously reported morphological classification method. The onco-immunological and morphologic characteristics of the tumors such as lymphoid follicle formation and interstitial fibrous hyperplasia, patient's peripheral blood lymphocyte subtypes and prognosis data were collected. The relationship between various factors and their impact on prognosis were analyzed. Results: There were 117 patients, including 61 females and 56 males. The male to female ratio was 0.9∶1.0. The age of onset was 24-89 years (median 52 years). Primary sites included head and neck (68 cases), lungs (26 cases), stomach (15 cases), and others (eight cases). Morphologically, 54 cases were type Ⅰ, 62 cases were type Ⅱ, and one case could not be classified. The onco-immunological and morphologic features of the LELC tumors showed a continuous spectrum. Interstitial TILs were noted from focally to diffuse, and the interstitial fibrous tissues were from hardly visible to obvious sclerotic. Formation of lymphoid follicles was seen in 42 patients; obvious fibrosis was seen in 31 cases. Data of peripheral blood lymphocyte subtyping by flow cytometry were available in 73 cases. These data included CD3+total T cells, CD3+CD4+helper T cells, CD3+CD8+cytotoxic T cells, CD3-CD56+natural killer (NK) cells, CD3-CD19+B cells, CD4+CD45RA-T helper induction subgroup, CD4+CD45RA+ T suppression induction subgroup, CD4+CD45RO+memory T cell subgroup, CD45RA+CD45RO+activated T cell subgroup, CD8+CD38+activated cytotoxic T cell, and CD25+lymphocytes and CD44+lymphocyte. The proportion of lymphocytes of each subtype was normal in most patients, but the proportion of CD44+lymphocytes in 61 cases (83.6%) was increased; the proportion of T cell suppression induced subgroups was decreased in 53 cases (72.6%). Correlation analysis found a significant correlation between clinical stage and NK cells (P=0.023); tumor histologic type and cytotoxic T cells were significantly positively correlated (P=0.012); while tumor cell morphologic differentiation was significantly related to total T cells (P=0.003) and NK cells (P=0.026); Formation of interstitial lymphoid follicles was positively correlated with memory T cell subsets (P=0.025); Tumor interstitial fibrosis was significantly positively correlated with T suppression-induced subpopulations (P=0.004), and was significantly negatively correlated with total T cells (P=0.023) and with the expression of CD44 adhesion molecules (P=0.003). Survival analysis found that lymphoid follicle formation was a favorable prognostic factor for LELC (P=0.001). Conclusions: The onco-immunological and morphologic features in LELC show a continuous spectrum; the tumor clinicopathological characteristics and onco-immunological morphology are closely related to peripheral blood T lymphocyte subtypes, and the formation of interstitial lymphoid follicles is a favorable prognostic factor for LELC.

[Pathological features related to onco-immunity and their clinical significance of pancreatic ductal adenocarcinoma].

Objective: To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-Ⅰ, PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. Results: There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3+T cells were deficient in 124 cases (124/192, 66.31%). CD8+T cells were deficient in 152 cases (152/192, 79.58%). MHC-Ⅰ expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (P=0.035), perineural invasion (P=0.002), stage (P=0.004) and long-term alcohol consumption (P=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (P=0.002), and negatively with tumor differentiation (P=0.024). CD8+T cells were positively correlated with CD3+T cells (P=0.032), MHC-Ⅰ expression (P<0.001) and PD-L1 expression (P=0.001), and negatively correlated with long-term smoking (P=0.016). Univariate analysis showed that histological nonspecific type (P=0.013) and TII-N (P<0.001) were the factors for good prognosis. Vascular invasion (P=0.032), perineural invasion (P=0.001), high stage (P=0.003) and long-term alcohol consumption (P=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. Conclusions: TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.

[Research progress in the treatment of refractory temporal lobe epilepsy based on stereotactic-electroencephalogram].

Temporal lobe epilepsy, with a variety of etiological, symptomatic, electrophysiological characteristics, has the highest incidence among all focal epilepsy, and a high rate of progression to refractory epilepsy. Surgery is an effective treatment, but traditional methods are usually difficult to accurately locate the epileptogenic zone, which may be resolved by stereotactic-electroencephalogram(SEEG) technique. Radiofrequency thermocoagulation and MRI-guided laser interstitial thermal therapy based on SEEG provide a new accurate and minimally invasive choice for refractory epilepsy patients with high surgical risk and difficulty.

[Correlation analysis of low-dose X-ray ionizing radiation and thyroid function in radiation workers].

Objective: To investigate the effect of low-dose X-ray ionizing radiation on thyroid function of radiation workers. Methods: From January to December 2021, a total of 1039 medical workers in some tertiary hospitals in Wuhan were selected as the survey subjects, of which 518 radiation workers were selected as the exposure group, and 521 non-radiation workers were selected as the control group. The general conditions of the two groups were collected, and 5 indicators of thyroid function were measured, including total thyroxine (TT(4)) , total triiodothyronine (TT(3)) , free triiodothyronine (FT(3)) , thyroid stimulating hormone (TSH) , and free thyroxine (FT(4)) . The annual cumulative dose of ionizing radiation exposure in the exposure group was collected. Pearson χ(2) test and independent sample t test were used to compare the general conditions, 5 indicators of thyroid function and abnormal rate between the two groups. Linear regression model was used to analyze the correlation between the annual cumulative dose and 5 indicators of thyroid function in the exposure group. Binary logistic regression was used to analyze the influencing factors of thyroid dysfunction in the exposure group. Results: The TT(4) levels of the workers in the control group and the exposure group were (7.95±1.07) µg/dl and (8.26±1.41) µg/dl, respectively, and the FT(4) levels were (16.33±2.19) pmol/L and (17.15±2.42) pmol/L, respectively, the rate of thyroid dysfunction was 4.80% (25/521) and 8.49% (44/518) , and the above differences were statistically significant (P<0.05) . Linear regression analysis showed that the annual cumulative dose of the exposure group was significantly correlated with TT(4), TT(3), FT(4), and TSH (P<0.05) . For every 1 mSv increase in the annual cumulative dose, TT(4) increased by 1.661 µg/dl, FT(4) increased by 1.422 pmol/L, TT(3) decreased by 0.113 ng/ml, and TSH decreased by 0.731 µIU/ml. Binary logistic regression analysis showed that the older the radiation workers, the higher the risk of thyroid dysfunction (OR=1.080, 95% CI: 1.016-1.148, P=0.013) ; the greater the annual cumulative dose, the higher the risk of thyroid dysfunction (OR=6.400, 95%CI: 1.796-22.811, P=0.004) . Conclusion: The annual cumulative dose of low-dose X-ray ionizing radiation is positively correlated with thyroid function TT(4) and FT(4) of radiation workers, and negatively correlated with TT(3) and TSH; the greater the age and annual cumulative dose, the higher the risk of thyroid dysfunction.

[Prognostic value of new TNM staging and serum CA125 in malignant peritoneal mesothelioma].

Objective: To explore the relationship between the new Tumor-Node-Metastasis (TNM) staging system and the serum CA125 level with the prognosis of malignant peritoneal mesothelioma (MPeM) . Methods: The clinical data of 74 patients with MPeM diagnosed by pathology and immunohistochemistry were collected from January 2005 to June 2016 in Cangzhou Central Hospital. According to the results of CT-peritoneal carcinoma index (PCI) , the tumor load was divided into T1 (PCI 1-10) , T2 (PCI 11-20) , T3 (PCI 21-30) and T4 (PCI 31-39) , combined with lymph node metastasis and extraperitoneal metastasis, a new TNM staging system was established. And serum CA125 level was measured in the same time. The median survival time of patients with MPeM, the effect of the new TNM staging system, and serum CA125 levels on their prognosis were retrospectively analyzed. Results: Among the 74 patients with MPeM, 25 (33.8%) cases were males and 49 (66.2%) cases were females. There were 8 cases with systemic chemotherapy, 8 cases with heated intraperitoneal chemotherapy, and 1 case with combination chemotherapy. 10 cases were T1, 22 cases were T2, 27 cases were T3, 15 cases were T4, 12 cases had lymph node metastasis and 10 cases had distant metastasis. The median survival time of T1, T2, T3 and T4 were 12, 10, 6 and 3 months respectively. There were 38 (77.6%) cases with high serum CA125 in all 49 cases who have been tested for CA125. The median survival time of positive group and negative group were 6 months and 11 months respectively. 68 (91.9%) patients had died by the end of collecting data. The median survival time was 8 months. Univariate analysis showed that there were significant differences in survival time between patients with different CT-PCI stages, serum CA125 levels, and with or without lymph node and extraperitoneal metastasis (P<0.05) . Multivariate analysis showed that CT-PCI was independent risk factors for the prognosis of MPeM (HR=2.203, 95%CI: 1.475-3.289) . Conclusion: The new TNM staging system and serum CA125 are important for the prognosis of patients with MPeM. Early detection, early diagnosis and comprehensive treatment can improve the survival time of patients with MPeM.

[The association of Vitamin D levels with lipid metabolism during pregnancy].

Vitamin D deficiency is common in pregnant women, and it is associated with multiple gestational complications, fetal intrauterine dysplasia, and maternal and infant health in postpartum period. Vitamin D involved in lipid metabolism may affect maternal-fetal health during pregnancy through this biological pathway. This review provides an overview of three main aspects, including, the effect of vitamin D on the mechanism of lipid metabolism, the relationship between vitamin D and lipid metabolites in pregnant women and women with pregnancy complications. An association between vitamin D status and lipid metabolism at different stages of pregnancy has been justified in most current studies, and the underlying mechanism has also been partly elucidated. Given some gestational complications, such as gestational diabetes and pre-eclampsia, pregnant women with these conditions are often associated with abnormal lipid metabolism and vitamin D deficiency. There is no doubt that the studies on the vitamin D supplementation and lipid metabolism improvement could have crucial clinical significance for this population. More randomized controlled trials with multi-center, large sample and multi-dose interventions are needed in the future to provide scientific evidence for clinical practice.

[Trends analysis of vitamin D status among pregnant women in Hefei during 2015-2017]. / 2015­2017å¹´åˆè‚¥å¸‚å­•å¦‡ç»´ç”Ÿç´ DçŠ¶æ€å˜åŒ–è¶‹åŠ¿ç ”ç©¶

From March 2015 to February 2018, 4 728 women aged 18 to 45 years old with single-pregnancy at the gestational age of 13 to 27 weeks in Hefei were recruited to analyze the trend of vitamin D status. The average levels of serum 25(OH)D in 2015, 2016 and 2017 were (43.22±18.41) nmol/L, (39.3±15.1) nmol/L and (36.6±17.0) nmol/L, and the prevalence of vitamin D deficiency were 69.5%, 77.6% and 81.4%, respectively. Compared with 2015, the levels of serum 25(OH)D in pregnant women in 2016 and 2017 decreased by 5.23 (95%CI: 4.10-6.35) nmol/L and 7.98 (95%CI: 6.77-9.19) nmol/L. The OR (95%CI) values for the risk of vitamin D deficiency were 1.88 (95%CI: 1.57-2.24) and 2.41 (95%CI: 1.98-2.93).

[Prospective cohort study on association between peri-conceptional air pollution exposure and gestational diabetes mellitus].

Objective: To explore the association between the exposure to major air pollutants in pre-pregnancy and early pregnancy (peri-conceptional period) and gestational diabetes mellitus (GDM). Methods: From March 2015 to April 2018, 4 817 pregnancies were recruited at three prenatal check-ups hospital in Hefei (Hefei First People's Hospital, Hefei. Maternal and Child Care Hospital and the First Affiliated Hospital of Anhui Medical University), China. Questionnaire was used to collect the demographic data, the health status and lifestyle of pregnant women. GDM was diagnosed according to the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2017 Edition). Logistic regression was used to investigate the association of exposure to major air pollutants (PM(2.5), PM(10), SO(2), CO and NO(2)) during different periods of pre-pregnancy (12 weeks before pregnancy) and first trimester (12 weeks after last menstruation) and duration of exposure to high levels of pollutants with GDM. Results: The mean±SD of the age of subjects was (29.14±4.19) years old and the prevalence of GDM was 21.4% (n=1 030). The results of multivariate logistic regression analysis showed that after adjusting for confounding factors, the risk of GDM increased gradually with the prolonged exposure time of high-concentration pollutants compared with pregnant women who were not exposed to high pollution during the pre-pregnancy (χ(2)=61.28, P(trend)<0.001) with the OR (95%CI) values for exposure time of 1, 2, and 3 months about 1.42 (1.10-1.84), 1.73 (1.29-2.33), and 2.51 (1.75-3.59), respectively. In the pre-pregnancy period, in every 10 µg/m(3) increase of PM(2.5) and PM(10), the OR (95%CI) values of GDM were 1.14 (1.08-1.20) and 1.13 (1.08-1.19), respectively; for each increase of 1 µg/m(3) and 0.10 mg/m(3) of SO(2) and CO, the OR (95% CI) values of GDM were 1.03 (1.01-1.05) and 1.07 (1.01-1.13), respectively. For every 1 µg/m(3) increase in the average concentration of SO(2) in the first trimester, the OR (95%CI) value of GDM was 1.02 (1.01-1.05). Conclusion: PM(2.5), PM(10), SO(2) and CO exposure during the pre-pregnancy and SO(2) exposure in first trimester were positively correlated with the risk of GDM.

[Relationship between morphological characteristics and prognosis of non-nasopharyneal EBV-associated carcinoma].

Objective: To analyze the pathological features and their influence on the clinical outcome of non-nasopharyngeal EBV-associated carcinomas. Methods: One hundred and twenty cases of non-nasopharyngeal EBV-associated carcinoma confirmed by in situ hybridization were identified at Zhejiang Cancer Hospital from January 1, 2006 to May 1, 2018, and the clinicopathological data were collected and analyzed using Kaplan-Meier survival analysis, Cox univariate and multivariate analysis. Results: One hundred and twenty cases were involved in the study; the male to female ratio was 1∶1; patients' age range was 24 to 89 years (median 50 years). The primary sites were large parotid glands (62 cases), lung(26 cases), stomach(15 cases), and others (oral, oropharynx, larynx, cervix, liver; totally 17cases). Non-nasopharyngeal EBV-associated cancer could be divided into two histological types according to the amount of interstitial lymphocytes: type Ⅰ was "lymphoepithelial-like carcinoma" and rich in stromal lymphocytes; type Ⅱ lacked lymphocytic infiltration. Ninety-eight primary tumor samples could be classified morphologically: 43 cases were as type Ⅰ and 55 cases as typeⅡ; the distribution of type Ⅰ was 57.4% (27/47) in large parotid glands, 20.8% (5/24) in lung, 4/13 in stomach, and 7/14 in other sites. Complete treatment and survival data were obtained for 114 patients. According to the TNM staging criteria of WHO, 52 patients were at early stages (Ⅰ-Ⅱ) and 62 were at advanced stages (Ⅲ-Ⅳ); 102 patients underwent surgery. Seventy-four patients received adjuvant chemotherapy before or after surgery, and 52 patients received local radiotherapy. Kaplan-Meier survival analysis showed that patients with type Ⅱ EBV-associated carcinoma had a worse prognosis than patients with type Ⅰtumors (P=0.010 2). In addition, vascular invasion(P=0.021 8),neural recidivism(P=0.000 1),advanced stage(P=0.017 1),lymph node metastasis (P=0.005 0) and chemotherapy (P=0.013 2) were poor prognostic factors; female patients had better survival than male (P=0.028 4). Cox multivariate regression analysis found that lymph node metastasis (95%CI: 1.489-13.830, P=0.007 6) and neural recidivism (95%CI: 1.228-6.544, P=0.014 7) were independent adverse prognostic factors. Cox multivariate regression analysis after stratification by site revealed that radiotherapy was a preferable prognostic factor for EBV-associated carcinoma of the large salivary glands (95%CI: 0.003-0.569, P=0.016 8). Conclusion: EBV associated carcinoma can be divided into two types, for which type Ⅰ was with abundant interstitial lymphocytes and type Ⅱ was lack of interstitial lymphocytes. TypeⅡ EBV-associated carcinoma has a worse prognosis than type Ⅰ. Radiation therapy can prolong the survival time of patients with primary EBV-associated carcinoma of large salivary glands.

[Survival of patients with primary central nervous system diffuse large B-cell lymphoma: impact of gene aberrations and protein overexpression of bcl-2 and C-MYC, and selection of chemotherapy regimens].

Objective: To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Methods: Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER). Copy number variation (ICN) and translocation status of bcl-6, bcl-2 and C-MYC genes were detected by fluorescence in situ hybridization (FISH). The relationship between the above indexes and the prognosis was analyzed by univariate, bivariate survival analysis and multiple Cox hazard regression analysis. Results: The study included 33 patients of PCNS-DLBCL, without evidence of primary or secondary immunodeficient disease. Male to female ratio was 1.36∶1.00, and the average age was 56 years. Twenty cases had single lesion while 13 had multiple lesions. Deep brain involvement was seen in 12 cases. All patients underwent partial or total tumor resection. Five patients received whole brain post-surgery radiotherapy, nine patients received high-dose methotrexate (HD-MTX) based chemotherapy, and 12 patients received whole-brain radiotherapy combined with HD-MTX based chemotherapy. Severn patients received no further treatment and rituximab was used in 8 patients. According to the Hans model, 27 cases were classified as non-GCB subtypes (81.8%). Bcl-2 was positive in 25 cases (75.8%, 25/33) and highly expressed in 8 (24.2%). MYC was positive in 12 cases (36.4%) and double expression of bcl-2 and MYC was seen in 6 cases. EBER positive rate was 10.0%(3/30), all of which had multiple lesions. Two bcl-6 gene translocations and 3 amplifications were found in 28 patients. Two translocations, 3 ICN or with both bcl-2 gene translocation and ICN were found in 30 patients. Four ICNs of C-MYC gene were found in 28 patients. Elevated protein in cerebrospinal fluid (CSF) was found in 13 patients. LDH increased in 10 cases. Follow-up period was 2-90 months with the average survival time of (23.0±3.7) months and two-year survival rate of 39.0%. Univariate survival analysis showed that overexpression of bcl-2 protein (≥70%) and MYC protein (≥40%), bcl-2 gene abnormality (including copy number increase and translocation), C-MYC gene copy number increased were adverse factors for survival. C-MYC/ bcl-2 gene double hit was seen in 2 cases. Bivariate survival analysis found that of bcl-2/MYC protein double expression and bcl-2 and C-MYC genes double aberration were significantly associated with adverse outcomes. Cox multivariate risk regression analysis found that gender, cerebrospinal fluid protein increasing, and ICN of C-MYC gene were independent poor prognostic factors. DH-MTX based comprehensive chemotherapy was associated with better prognosis. Conclusions: Double hit at genomic level (copy number variations and gene rearrangements) and double protein expression of bcl-2 and C-MYC in PCNS-DLBCL are significantly associated with an adverse outcome. DH-MTX based comprehensive treatment may prolong the patient survival.

[Effects of L-asparaginase on proliferation, cell cycle and apoptosis of Burkitt lymphoma cell lines].

Objective: To investigate the effect of L-asparaginase on the proliferation, cell cycle, and apoptosis of Burkitt lymphoma cell lines and explore the molecular mechanism. Methods: The effect of L-asparaginase on the cell proliferation of Burkitt lymphoma cell lines was detected using the CCK-8 method. The apoptosis rate and cell cycle were detected using flow cytometry. The expression of related molecules in cell cycle, apoptosis, autophagy, and PI3K/Akt/mTOR signaling pathway was detected and analyzed using qPCR and Western blot assay. Results: L-asparaginase significantly inhibited the proliferation of Burkitt lymphoma cell lines and caused cell cycle arrest at G(0)/G(1) phage. L-asparaginase induced cell apoptosis and autophagy in Burkitt lymphoma cell lines. Further results showed that L-asparaginase inhibited the expression of c-Myc and also inhibited the expression of p-PI3K, p-Akt-S473, p-mTOR, p-70S6K, and p-4E-BP1. Combining PI3K inhibitor LY294002 with L-asparaginase further induced apoptosis. Additionally, L-Asp inhibited STAT and ERK signaling pathways. Conclusion: L-asparaginase inhibited Burkitt lymphoma cell proliferation, arrested cell cycle, activated autophagy, and induced apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway.

[Correlation between BRAP expression and prognosis of patients with laryngeal squamous cell carcinoma].

Objective:To investigate the expression of BRCA1 associated protein（BRAP） and its correlations with clinicopathological features and prognosis of patients with laryngeal squamous cell carcinoma（LSCC）. Method:The protein expression of BRAP in LSCC tissues and normal laryngeal tissues were assessed by immunohistochemistry and Western blot, and their correlations with clinicopathological features and prognosis were statistically analyzed. Result:The expression of BRAP in LSCC was significantly higher than that in normal laryngeal tissues（P<0.05）. BRAP expression was significantly correlated with the TNM stage and lymph node metastasis（P<0.05）. Kaplan-Meier survival analysis showed that LSCC patients with high BRAP expression had worse overall survival than those with low BRAP expression（P<0.01）. Multivariate Cox proportional-hazards analysis showed that the high expression of BRAP protein was an important poor prognostic indicator of the patients. Conclusion:BRAP is related with the development of LSCC, and it may be used as an important prognostic biomarker for LSCC patients.

[Association between vitamin D level and lipid metabolism during second trimester].

Objective: To explore the relationship between the vitamin D levels and lipid metabolism during second trimester. Methods: A total of 1 875 pregnant women who were in the second trimester and had antenatal care in 3 hospitals in Hefei of Anhui province from March 2015 to February 2018 were included. Baseline questionnaire survey was performed, and fasting venous blood samples were collected from the pregnant women to detect serum 25(OH)D, cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels. Cubic non-linear model and linear regression model were used to analyze the linear relationship between vitamin D levels and lipid metabolism indicators in the second trimester. Results: The vitamin D deficiency rate was 75.3% (1 412/1 875) in the pregnant women. The mean levels of lipid metabolism indicators TC, TG, HDL-C and LDL-C were (233.22±38.87), (226.24±83.88), (79.04±12.77), and (109.54±25.95) mg/dl respectively. Multivariate linear regression model results showed, compared with Q5 of the 25(OH)D, the TC and TG levels of Q1-Q4 groups significantly increased, and the LDL-C of Q1 and Q2 groups significantly increased. The highest difference between TC, TG and LDL-C was observed in Q1 group. (TC: ß=16.88, 95%CI: 10.50-23.26; TG: ß=34.92, 95%CI: 21.32-48.53; LDL-C: ß=9.06, 95%CI: 4.77-13.35). No significant differences in HDL-C level among the 5 groups were observed. When stratified with vitamin D deficiency the results showed that, when 25(OH)D was <50 nmol/L, TC, TG and LDL-C levels decreased by 3.53 (95%CI: 1.30-5.75), 7.42 (95%CI: 2.41 to 12.44) and 2.08 mg/dl (95%CI: 0.60-3.57) along with a 10 nmol/L increase of 25(OH)D, the difference was statistically significant, and when 25(OH)D was ≥50 nmol/L, no significant correlation was found between 25(OH)D level and TC, TG and LDL-C levels. No significant relationship between 25(OH)D level and HDL-C level was observed regardless of vitamin D deficiency. Conclusions: There was a nonlinear relationship between vitamin D levels and lipid metabolism indicators in the second trimester. There was a significant negative correlation between 25(OH)D level and lipid metabolism indicators only in the deficiency of vitamin D.

[Influence of postoperative infection on hospitalization day and medical costs of patients with nervous system tumor].

Objective: To investigate the influence of postoperative infection on average hospitalization days and medical costs in patients with nervous system tumor. Methods: The tumor patients treated in neurosurgery ward from July 1, 2015 to June 30, 2017 were included in the study. The patients with and without postoperative infections were divided into a case group and a control group, respectively (1 ∶ 1 ratio), matched by admission time (±3 months), age (±5 years) and surgical site. Average hospitalization days and medical costs between the two groups were analyzed. Results: The incidence of postoperative infection was 5.66%, the surgical site infection and lower respiratory tract infection accounted for 54.72% and 31.32% of the total, respectively. The median of hospitalization days in the case group was 20.5, 8.5 days longer than that in the control group (Z=-10.618, P<0.001). The median of total medical costs in the case group was 91 573.42 yuan, higher than that of the control group by 30 518.17 yuan (Z=-9.988, P<0.001). The average costs of surgical and lower respiratory tract infection were 84 888.50 yuan and 110 442.64 yuan, respectively. Among them, surgical site infection or lower respiratory tract infection caused the extra cost of 23 627.49 yuan (Z=-6.627, P<0.001) and 43 631.36 yuan (Z=-4.954, P<0.001), respectively. Conclusions: Postoperative infection greatly increased the patient's financial burden, prolonged the hospitalization duration and resulted in unnecessary use of health resources. It is necessary to pay close attention to postoperative infection.

Correlation between HSD17B4 expression in rat liver cancer tissues and inflammation or proliferation.

OBJECTIVE: Pathogenesis and progression of liver cancer are correlated with inflammatory response and estrogen level. 17ß-estradiol dehydrogenase IV (HSD17B4) is highly expressed in human liver cancer tissues. HSD17B4 participates in liver cancer cell proliferation via suppressing estradiol (E2) activity. This study generated a rat liver cancer model, on which the correlations between HSD17B4 and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), proliferating cell nucleus antigen (PCNA) expression were analyzed. MATERIALS AND METHODS: Male Sprague Dawley (SD) rats were randomly assigned into control and model group (N=30). Diethylnitrosamine was used to induce liver cancer in a rat model. HE staining was used to observe liver injury whilst ELISA was used to measure serum TNF-α and IL-6 levels. The level of serum E2 was quantified by radioimmunoassay. Serum liver function indexes were measured by automatic biochemical analyzer. Protein expressions of HSD17B4, p-Akt, p-ERK and PCNA were measured by Western blot. RESULTS: The inflammatory infiltration and necrosis of hepatocytes were shown in model group by HE staining, along with aggravated liver indexes. Significantly high phosphorylation level of Akt and ERK, along with the increase of HSD17B3 and PCNA expressions, was found in model group (p<0.05 compared to control group). Serum E2 level was statistically decreased, whilst TNF-α and IL-6 were up-regulated (p<0.05). HSD17B4 was positively correlated with TNF-α, IL-6 and PCNA expressions (r=0.68, 0.62 and 0.56, p<0.05). CONCLUSIONS: HSD17B4 is over-expressed in rat liver cancer tissues. Its expression was positively correlated with TNF-α, IL-6 and PCNA levels, and probably participates in liver cancer cell proliferation via ERK and Akt signal pathway.