[Clinical and prognostic features of ovarian endometrioid carcinoma with synchronous endometrial lesions].

Objective: To compare the clinical and prognostic characteristics of ovarian endometrioid carcinoma (OEC) patients with synchronous endometrial lesions and patients with pure OEC. Methods: A retrospective review of the medical records of patients received initial treatment and a postoperative pathological diagnosis of OEC at Peking University People's Hospital between August 1998 and December 2017 were performed. According to the inclusion criteria, a total of 56 patients with OEC were included in the study, including 13 patients concurrent with simultaneous endometrial lesions (Group A) and 43 patients with pure OEC (Group B). Results: Patients with synchronous endometrial lesions accounted for 23% (13/56). Mean age of Group A at diagnosis was (44.9±8.3) years old, 2/13 of patients were postmenopausal, and no one had a history of hypertension, the first symptom of 5/13 people was irregular vaginal bleeding. Mean age of Group B patients at diagnosis was (52.7±10.2) years old, 53% (23/43) of patients were postmenopausal, and 28% (12/43) patients had the history of hypertension, the first symptom of 4 (9%, 4/43) people was irregular vaginal bleeding. The differences of age, menopause status, history of hypertension and initial symptoms between the two groups were statistically significant (all P<0.05). There were no significant differences in fertility history, dysmenorrhea history, age of menarche, history of endometriosis, preoperative and postoperative CA125 level, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor grade, metastatic site and platinum-based chemotherapy drug resistance between the two groups (all P>0.05). The overall 5-year survival rate of OEC patients was 91.6%, and the overall 5-year progression-free survival rate was 76.6%. Among them, the 5-year survival rate of the OEC concurrent with simultaneous endometrial lesions group was 80.2%, and the pure OEC group was 93.4%; the 5-year progression-free survival rate of the OEC concurrent with simultaneous endometrial lesions group was 74.1%, and the 5-year progression-free survival rate of the pure OEC group was 77.3%. There were no significant differences between the two groups (all P>0.05). Multivariate analysis showed that the independent factors for the prognosis of OEC patients were FIGO stage (P=0.006) and residual lesion size (P=0.020). Conclusions: OEC patients have a high proportion of simultaneous endometrial lesions. OEC with simultaneous endometrial lesions are younger than patients with pure OEC. Synchronous endometrial lesions do not affect the prognosis of patients with OEC.

[Distributed lag effects on the relationship between daily mean temperature and the incidence of bacillary dysentery in Lanzhou city].

OBJECTIVE: To discuss the lag effects of daily average temperature on the daily cases of bacillary dysentery in Lanzhou city. METHODS: The data of daily cases of bacillary dysentery were collected during 2008 and 2015 in the city, and the meteorological data at the same period was integrated. The distributed lag non-linear model was used to analyze the relevance between daily average temperature and the daily cases of bacillary dysentery. RESULTS: The exposure response relationship between the daily temperature and the incidence of bacillary dysentery was "J" type, the lowest incidence temperature was 17 °C, and the effect of high temperature on different gender and age groups was higher than that of the intermediate effect. The effect of high temperature and intermediate effect on the male and female groups showed an acute effect, the effect of the day was the highest, followed by fluctuations in temperature, and the greater the impact on women. In different age groups, high temperature effect and the intermediate effect of bacterial dysentery in 0-3 years old groups were the biggest; the effects of high and intermediate temperature on people aged 0-3 and 19-64 year all showed acute effects, which were the maximum value at the day, then decreased volatility; and for people aged over 65 years, the day after the onset, decreases and then increases slowly. There were obviously increasing risks of bacillary dysentery both the high temperature (32 °C) and the middle temperature (26 °C) with respect to 17 °C. The accumulative effects were highest at lag14 days, and the RR (95%CI) values of middle temperature was 2.30 (1.53-3.13), 2.45 (1.65-3.30), 2.41 (1.59-3.28), 2.54 (1.40-3.79), 1.82 (0.41-3.43), 1.98 (1.11-2.93), and 1.73 (0.68-2.88) among the males, females, 0-3 years old, 4-11 years old, 12-18 years old, 19-64 years old and over 65 years old people, respectively; while the high temperature was 2.93 (1.38-4.69), 3.08 (1.48- 4.90), 3.26 (1.60-5.16), 3.12 (1.06-5.56), 1.94 (0.73-5.39), 2.31 (0.54-4.36), and 2.06 (0.02-4.51), respectively. CONCLUSION: The high temperature may increase risks of bacillary dysentery, and the females and younger people were the sensitive population. Meteorological factors play an important role in the occurrence and development of bacillary dysentery in Lanzhou. The incidence of bacillary dysentery is affected by multiple meteorological factors, but the primary one is high temperature. The temperature has not a direct effect on the incidence of bacillary dysentery, but an indirect influence in different populations through the impacts of various aspects of the incidence of bacterial dysentery (residents living habits, communication channels and the habits of the susceptible population).

[Tumor derived IgG suppress the proliferation of T cells in cord blood].

OBJECTIVE: To explore the function of tumor derived IgG (tIgG) and whether the tIgG can inhibit T cells activity. METHODS: The tIgG was purified from ovarian cancer tissue. The cord blood monocyte cells (CBMC) and cord blood lymphocyte (CBL) were isolate from human umbilical cord blood. The CBMC and CBL were stimulated with phytohaemagg lutinin (PHA) in order to let the CBMC and CBL in the state of proliferation. Carboxyfluorescein succinimidyl amino ester (CFSE) was cultured with CBMC and CBL. CFSE had no cell toxicity, which could penetrate through the cell membrane and combine the intracellular protein. The fluorescence intensity decreased with the proliferation of cells step by step, so the proliferation of these cells could be detected in flow ctytometry. The tIgG which was purified from ovarian cancer tissue was divided into three groups, 1 mg/L group, 10 mg/L group, and 100 mg/L group, and the intravenous immunoglobulin (IVIG) was also divided into three groups too. The CBMC and CBL were treated by tIgG with 1 mg/L, 10 mg/L, and 100 mg/L in order to observe the proliferation of T cells. The cells were treated with IVIG as a positive control group, and the cells were treated with phosphate buffer saline (PBS) as a negative control. The proliferation of CD4+ or CD8+ T cells were detected in CBMC and CBL. The proliferation of the T cells in CBMC and CBL after 64 h and 86 h were detected. RESULTS: In the system of CBMC, the tIgG could suppress the proliferation of CD4+ or CD8+ T cells. The results could also be found in the system of CBL. The CD4+ or CD8+ T cells in the group which were treated with PBS were more active than those in the group which were treated with tIgG and IVIG. The suppression in the group which were treated with tIgG, was stronger than that in the group treated with IVIG. In addition, the suppression of T cells in the group which were stimulated with tIgG as 100 mg/L was more effective than that in the group which were stimulated with tIgG as 10 mg/L. This could prove that tIgG had the function of immunomodulation. CONCLUSION: The tIgG can be involved in immune escape of cancer.

[Experiment research of natural killer cells amplification in vitro and the killing effect on ovarian cancer cells].

Objective: To amplify natural killer (NK) cells in vitro and explore its killing effect on ovarian cancer cells. Methods: (1) The separation of NK cells and identification. A total of 20 ml peripheral blood of one healthy volunteer was collected in Nov. 2015, Peking University People's Hospital. The peripheral blood mononuclear cells of normal volunteers were isolated, cultured in vitro and amplificated cultivation for 14 days with K562 cells transfected and expressing interleukin 21 (IL-21-K562) as nourish cells. The number and dynamic state of the growth cells were monitored during the cultured process. Cells were harvested and counted after 14 days cultured. The NK cells phenotypes were detected by flow cytometry. (2) The killing effect of NK cells on ovarian cancer cells: the ratio of effector cells (NK cells) and target cells (ovarian cancer cells and its control) was 50∶1, 20∶1, 10∶1, 5∶1 or 1∶1, NK cells killing effect on ovarian cancer cells was detected by the lactate dehydrogenase (LDH) release experiments. Results: (1) The results of NK cells establishment and phenotypic characterization: the cells were induced in vitro for 14 days by amplification culture. With the extension of incubation time, the number of NK cells increased constantly, from 2.0×10(7) on day 0 to 5.1×10(9) on day 14. Obvious amplification of the total number of cells were detected for 255 times. Living cells unstained by trypan blue eventually reached 95% above. Before and after the induction and amplification in vitro, the percentage of NK cells(CD(3)(-)CD(5)(6+)cells) in CD(3)- cells were 2.33% and 85.32%, respectively (P<0.01), which covered the whole lymphocytes 1.06% and 69.42%, respectively (P<0.01), which showed that NK was the main cell type in the amplificated lymphocytes. (2) The killing rate of NK cells on ovarian cancer cells in vitro: the results detected by LDH release experiments showed that NK cells could performed strong nonspecific killing effect on ovarian cancer cell lines SKOV3, HOC1A, 3AO and CAOV3, as well the normal ovarian cell line T29 and NK sensitive cell line K562, and the killing effect increased significantly along with the increase of effector cells and target cells ratio (P<0.01). When the ratio was 1∶1, the killing rate was 37% for K562, while the rate of killing of other cells was around 10% (P<0.05). When the effect-target ratio was 20∶1 and 50∶1, in addition to CAOV3 cells (more than 70%), NK cells had a kill rate of more than 80% for other ovarian cancer cells lines and their control cell K562 and T29 cells (P>0.05). Conclusion: NK cells could be established in vitro and have a good non-specific killing effect on ovarian cancer cells.

Nickel oxide nanoparticles induced pulmonary fibrosis via TGF- ß1 activation in rats.

Nano nickel oxide (NiO), widely used in industry, has recently been discovered to have pulmonary toxicity. However, no subchronic exposure studies about nano NiO-induced pulmonary fibrosis have been reported. The objective of this study was to investigate pulmonary fibrosis induced by nano NiO and its potential mechanism in rats. Male Wistar rats ( n = 40, 200-240 g) were randomized into control group, nano NiO groups (0.015, 0.06, and 0.24 mg/kg), and micro NiO group (0.024 mg/kg). All rats were killed to collect lung tissue after intratracheal instillation of NiO particles twice a week for 6 weeks. To identify pulmonary fibrosis, Masson trichrome staining, hydroxyproline content, and collagen protein expression were performed. The results showed widespread lung fibrotic injury in histological examination and increased content of hydroxyproline, collagen types I and III in rat lung tissue exposed to nano NiO. To explore the potential pulmonary fibrosis mechanism, transforming growth factor beta 1 (TGF- ß1) content was measured by enzyme-linked immunosorbent assay, and the messenger RNA expression of key indicators was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The TGF- ß1 content was increased in nano NiO exposure groups, as well as the upregulated gene expression of TGF- ß1, Smad2, Smad4, matrix metalloproteinase, and tissue inhibitor of metalloproteinase. The findings indicated that nano NiO could induce pulmonary fibrosis, which may be related to TGF- ß1 activation.

Residue depletion of decoquinate in chicken tissues after oral administration.

A rapid, sensitive, and reliable high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the analysis of decoquinate in chicken tissues. The compounds were extracted using acetonitrile by liquid-liquid extraction (LLE) and purified with an Oasis(™) HLB solid-phase extraction (SPE) cartridge. Chromatographic separation was performed on an XTerra C18 reversed-phase column with a mobile phase of water containing 0.1% formic acid and acetonitrile. The analyte was detected by tandem quadrupole mass spectrometry after positive electrospray ionization by multiple reaction monitoring. The detection and quantitation limits were 1 and 2.5 µg/kg, respectively. The recoveries of edible tissues ranged from 85.3% to 104.9%, with relative standard deviations (RSD) lower than 10.4%. The depletion profile of decoquinate was studied in healthy chickens after oral administration of feed containing 27.2 mg/kg decoquinate for 10 consecutive days. The residue concentrations of decoquinate in chicken muscle and liver were detected using the developed method. The highest residue concentrations were attained 0.25 day post-treatment, and decoquinate residues were still detected 5 days postmedication in the tissues examined. The developed method has been successfully applied to the depletion study of decoquinate in chicken tissues. The recommended withdrawal period with oral administration based on our research is 3 days.

The role of HE4 in ovarian cancer: inhibiting tumour cell proliferation and metastasis.

As a promising biomarker, human epididymis protein 4 (HE4) has been widely used for the early detection and differential diagnosis of ovarian cancer. This study evaluated the function of HE4 in the carcinogenesis and progression of ovarian cancer. An enzyme immunometric assay, used to detect HE4 in the serum of ovarian cancer patients, showed that the protein could discriminate between malignant and benign ovarian tumours with high specificity. An exogenous HE4 gene was transfected into ovarian cancer cell lines and an immortalized ovarian epithelial cell line. Compared with the controls, HE4 overexpression significantly promoted cell apoptosis and adhesion. Overexpression of HE4 also led to significant inhibition of cell proliferation, migration and invasiveness in vitro, as well as xenograft tumour formation in vivo. This is the first report to demonstrate the functional importance of HE4 in multiple cellular processes and indicates that HE4 may play a protective role in the progression of ovarian cancer.

The anti-tumor immune responses induced by a fusion protein of ovarian carcinoma anti-idiotypic antibody 6B11ScFv and murine GM-CSF in BALB/c mice.

Ovarian carcinoma anti-idiotypic antibody 6B11 was murine derived; we previously have cloned 6B11 single-chain Fv antibody (6B11ScFv) and constructed the 6B11ScFv/human granulocyte-macrophage colony stimulating factor (GM-CSF) fusion protein (designated as 6B11GM) to enhance the immunogenecity of the single-chain Ab(2). Because of the difference in species specificity between human GM-CSF and murine GM-CSF, there is no immune competent animal model on which the effect and metabolism of 6B11GM as a vaccine could be observed. In this study, 6B11mGM fusion gene was constructed by the fusing murine GM-CSF cDNA gene with 6B11ScFv. The fusion gene was cloned and expressed. The product of this gene is a fusion protein. It could specifically interact with the primary anti-ovarian carcinoma monoclonal antibody (COC166-9) and rat anti-mouse GM-CSF monoclonal antibody, respectively, and stimulate the growth of NFS-60 cells (a murine GM-CSF-dependent cell line). The specific anti-tumor immune response could be induced in BALB/c mice after immunized with anti-idiotypic fusion protein instead of ovarian carcinoma antigen without carrier proteins and adjuvant. Ab(3) could be detected in the sera of immunized mice with 6B11mGM by enzyme-linked immunoadsorbent assay test. Moreover, the fusion protein stimulated proliferation of CD4+ T cell from the spleen of BALB/c mice and proliferation of CD8+ T cell to a lesser degree. Therefore, 6B11mGM probably induces both humoral and cellular immunity against ovarian carcinoma in vivo.

Improved metastatic animal model of human prostate carcinoma using surgical orthotopic implantation (SOI).

BACKGROUND: An animal model demonstrating high metastasis of human prostate carcinoma is of importance in studying the biology and therapy of human prostate carcinoma Dr. Hoffman's group recently used surgical orthotopic implantation (SOI) of human prostate cells to nude mice to establish an animal model with high metastatic activity. To confirm the animal model by SOI reproducible in other laboratories and shorten the period requiring for the metastasis, we adopted SOI technique with a modification using PC-3M human prostate cell line which showed a higher metastatic activity than PC-3. MATERIALS AND METHODS: Intact tissue of the human prostate carcinoma cell line PC-3M was prepared by growth of this cell subcutaneous in a nude mouse. One piece of 1.5 mm3 intact tumor tissue was implanted by orthotopical surgery to the ventral lateral lobes of the prostate gland of 10 nude mice. Mice were sacrificed when they were found to be moribund. Metastasis in other tissues was evaluated by gross and microscopic morphology. RESULTS: All 10 mice showed the tumorigenesis in the prostate gland and metastasis of human prostate tumor cells into periaortic lymph nodes without other organ's metastasis. The time when mice with PC-3M SOI start moribund is 28-32 days after SOI. CONCLUSIONS: SOI is good technique to establish the efficiently metastatic animal mode. SOI using PC-3M human prostate cell line will leads to 100% metastasis of prostate tumor cells. So far, this model is much quicker and more efficient than those reported in literatures.