Recently, deep learning has achieved impressive results in medical image tasks. However, this method usually requires large-scale annotated data, and medical images are expensive to annotate, so it is a challenge to learn efficiently from the limited annotated data. Currently, the two commonly used methods are transfer learning and self-supervised learning. However, these two methods have been little studied in multimodal medical images, so this study proposes a contrastive learning method for multimodal medical images. The method takes images of different modalities of the same patient as positive samples, which effectively increases the number of positive samples in the training process and helps the model to fully learn the similarities and differences of lesions on images of different modalities, thus improving the model's understanding of medical images and diagnostic accuracy. The commonly used data augmentation methods are not suitable for multimodal images, so this paper proposes a domain adaptive denormalization method to transform the source domain images with the help of statistical information of the target domain. In this study, the method is validated with two different multimodal medical image classification tasks: in the microvascular infiltration recognition task, the method achieves an accuracy of (74.79 ± 0.74)% and an F1 score of (78.37 ± 1.94)%, which are improved as compared with other conventional learning methods; for the brain tumor pathology grading task, the method also achieves significant improvements. The results show that the method achieves good results on multimodal medical images and can provide a reference solution for pre-training multimodal medical images.
Humans ; Algorithms ; Brain/diagnostic imaging* ; Brain Neoplasms/diagnostic imaging* ; Recognition, Psychology

Hepatocellular carcinoma (HCC) is the most common liver malignancy, where HCC segmentation and prediction of the degree of pathological differentiation are two important tasks in surgical treatment and prognosis evaluation. Existing methods usually solve these two problems independently without considering the correlation of the two tasks. In this paper, we propose a multi-task learning model that aims to accomplish the segmentation task and classification task simultaneously. The model consists of a segmentation subnet and a classification subnet. A multi-scale feature fusion method is proposed in the classification subnet to improve the classification accuracy, and a boundary-aware attention is designed in the segmentation subnet to solve the problem of tumor over-segmentation. A dynamic weighted average multi-task loss is used to make the model achieve optimal performance in both tasks simultaneously. The experimental results of this method on 295 HCC patients are superior to other multi-task learning methods, with a Dice similarity coefficient (Dice) of (83.9 ± 0.88)% on the segmentation task, while the average recall is (86.08 ± 0.83)% and an F1 score is (80.05 ± 1.7)% on the classification task. The results show that the multi-task learning method proposed in this paper can perform the classification task and segmentation task well at the same time, which can provide theoretical reference for clinical diagnosis and treatment of HCC patients.
Humans ; Carcinoma, Hepatocellular ; Liver Neoplasms ; Learning

Background: New-generation adjuvants for foot-and-mouth disease virus (FMDV) vaccines can improve the efficacy of existing vaccines. Chinese medicinal herb polysaccharide possesses better promoting effects. Objectives: In this study, the aqueous extract from Artemisia rupestris L. (AEAR), an immunoregulatory crude polysaccharide, was utilized as the adjuvant of inactivated FMDV vaccine to explore their immune regulation roles. Methods: The mice in each group were subcutaneously injected with different vaccine formulations containing inactivated FMDV antigen adjuvanted with three doses (low, medium, and high) of AEAR or AEAR with ISA-206 adjuvant for 2 times respectively in 1 and 14 days. The variations of antibody level, lymphocyte count, and cytokine secretion in 14 to 42 days after first vaccination were monitored. Then cytotoxic T lymphocyte (CTL) response and antibody duration were measured after the second vaccination. Results: AEAR significantly induced FMDV-specific antibody titers and lymphocyte activation. AEAR at a medium dose stimulated Th1/Th2-type response through interleukin-4 and interferon-γ secreted by CD4+ T cells. Effective T lymphocyte counts were significantly elevated by AEAR. Importantly, the efficient CTL response was remarkably provoked by AEAR. Furthermore, AEAR at a low dose and ISA-206 adjuvant also synergistically promoted immune responses more significantly in immunized mice than those injected with only ISA-206 adjuvant and the stable antibody duration without body weight loss was 6 months. Conclusions These findings suggested that AEAR had potential utility as a polysaccharide adjuvant for FMDV vaccines.

Background: New-generation adjuvants for foot-and-mouth disease virus (FMDV) vaccines can improve the efficacy of existing vaccines. Chinese medicinal herb polysaccharide possesses better promoting effects. Objectives: In this study, the aqueous extract from Artemisia rupestris L. (AEAR), an immunoregulatory crude polysaccharide, was utilized as the adjuvant of inactivated FMDV vaccine to explore their immune regulation roles. Methods: The mice in each group were subcutaneously injected with different vaccine formulations containing inactivated FMDV antigen adjuvanted with three doses (low, medium, and high) of AEAR or AEAR with ISA-206 adjuvant for 2 times respectively in 1 and 14 days. The variations of antibody level, lymphocyte count, and cytokine secretion in 14 to 42 days after first vaccination were monitored. Then cytotoxic T lymphocyte (CTL) response and antibody duration were measured after the second vaccination. Results: AEAR significantly induced FMDV-specific antibody titers and lymphocyte activation. AEAR at a medium dose stimulated Th1/Th2-type response through interleukin-4 and interferon-γ secreted by CD4+ T cells. Effective T lymphocyte counts were significantly elevated by AEAR. Importantly, the efficient CTL response was remarkably provoked by AEAR. Furthermore, AEAR at a low dose and ISA-206 adjuvant also synergistically promoted immune responses more significantly in immunized mice than those injected with only ISA-206 adjuvant and the stable antibody duration without body weight loss was 6 months. Conclusions These findings suggested that AEAR had potential utility as a polysaccharide adjuvant for FMDV vaccines.

Objective:To evaluate the in vitro and in vivo immunostimulatory activity and the safety of ethanol extract of wild Artemisia rupestris L. (EEWAR). Methods:Bone marrow dendritic cells (BMDCs) from C57BL/6 mice were treated with different concentrations of EEWAR in vitro and the expression of CD40 and CD80 on BMDCs was detected by flow cytometry. ICR mice were subcutaneously immunized with different concentrations of EEWAR in combination with ovalbumin (OVA) or OVA alone. Aluminum adjuvant was used as the positive control. OVA-specific IgG antibodies in mouse serum samples were measured by ELISA following immunization. T cell proliferation in spleen tissues was detected by MTT method. Acute toxicity test was conducted in ICR mice to analyze the safety of EEWAR. Results:In vitro experiment showed that EEWAR at the concentrations of 10-20 μg/ml increased the expression of CD40 and CD80 on BMDCs ( P<0.05), and had no significant effect on the morphology of BMDCs; EEWAR at the concentrations of 100-200 μg/ml significantly promoted the expression of CD40 and CD80 on BMDCs ( P<0.01), but had a certain influence on the morphology of BMDCs. In vivo experiment showed that EEWAR enhanced the production of IgG, IgG 1 and IgG 2a antibodies against OVA and the proliferation of splenocytes ( P<0.05). In the acute toxicity test, EEWAR at the concentrations of 50-5 000 μg/ml had no side effects on mouse body weight and was relatively safe. Conclusions:EEWAR could promote the maturation of DCs and enhance the humoral and cellular immune responses when used as an adjuvant to OVA. It was safe in a certain dose range. This study provided reference for further research on EEWAR as a new-generation adjuvant.

Objective:To explore the immunomodulatory activity of ethanol extract of cultivated Cistanche deserticola (EECCD) in Xinjiang. Methods:Ovalbumin (OVA) was used antigen, ICR mice were divided into 9 g/L NaCl group (blank control group), EECCD group (1 200 μg EECCD), OVA group (10 μg OVA), low-dose EECCD/OVA group (400 μg EECCD+10 μg OVA), medium-dose EECCD/OVA group (800 μg EECCD+10 μg OVA), high-dose EECCD/OVA group (1 200 μg EECCD+10 μg OVA) and aluminum adjuvant (Alum)/OVA group (200 μg Alum+10 μg OVA). Mice were immunized subcutaneously, and the immunization was strengthened once 14 days after the initial immunization. The level of splenocyte proliferation was determined by thiazolyl blue tetrazolium bromide (MTT) method, and interferon γ (IFN-γ) and interleukin-4 (IL-4) in CD4 + T cell, dendritic cells (DCs) surface markers and CD4 +CD25 +Foxp3 + Treg were evaluated by fluorescence-activated cell sorting (FACS). Results:Three dose of EECCD can enhance OVA-specific IgG titers in serum. The antibody titer in medium-dose EECCD/OVA group was 250 000, which was the same as that in the Alum/OVA group. The medium-dose EECCD/OVA significantly improve IgG1 and IgG2a (both P<0.01). Therefore, the medium dose EECCD was selected as the best dose. MTT results displayed that splenocyte proliferation were significantly stimulated by medium-dose EECCD/OVA ( P<0.05), and the levels of IL-4 and IFN-γ in CD4 + T cells were promoted in groups administered with medium-dose EECCD/OVA (both P<0.01). Furthermore, medium-dose EECCD/OVA significantly up-regulated the levels of CD40, CD80, CD86 and major histocompatibility complex class Ⅱ (MHCⅡ) on DCs and down-regulated the frequency of CD4 +CD25 +Foxp3 + Treg (all P<0.05). Conclusions:EECCD has good immunomodulatory activity, can promote Th1-biased response, and has the therapeutic potential for the prevention of diseases.

Objective To investigate the efficacy of using Xinjiang wild Artemisia rupestris L. crude polysaccharides ( WARCP) as an immunologic adjuvant for influenza virus vaccine( IVV) .Methods ICR mice were subcutaneously immunized with 0.3 μg of IVV and 1.5 μg of IVV alone or co-administered with 200 μg of WARCP on 0 d and 14 d.Antibody levels in serum samples were detected by using indirect ELISA.MTT method was used to measure the proliferation of splenocytes.The growth conditions of mice were observed as well.Results No significant differences in the body weight were observed between mice from different groups (P>0.05).The levels of influenza virus-specific IgG, IgG1 and IgG2a were signifi-cantly increased in mice injected with WARCP adjuvant (P<0.05).The levels of IgG antibody in mice im-munized with low-dose of IVV and WARCP were significantly higher than those in mice immunized with high-dose of IVV alone (P<0.05), indicating at least 80% reduction in vaccine dosage by adding WARCP as adjuvant.Moreover, WARCP significantly promoted the proliferation of lymphocytes (P<0.05).Conclu-sion Adding WARCP to IVV enhanced the efficacy of IVV by boosting humoral and cellular immunity re-sponses with the advantages of high safety and dose-sparing.This study suggested the possibility of using WARCP as a novel immunologic adjuvant for influenza virus vaccine.

Objective To study the influence of seminal plasma reactive oxygen species(ROS),cell factors and sperm quality in infertile male with Uu infection and explore its action mechanism in male infertility.Methods Chose 83 cases of male in-fertility with Uu infection as the experimental group (Uu+ infertility group),30 cases of male infertility without Uu infec-tion (Uu- infertility group)and 30 normal men with children as a control (Normal fertility group).Respectively,determi-nate the levels of seminal plasma malondialdehyde (MDA),superoxide dismutase (SOD),IL-6,IL-10,IL-18 and TNF-α,and analyzed its correlation.Results In Uu+ infertility group,the levels of MDA (19.56±5.22 nmol/ml),IL-6 (58.31±8.94 pg/ml),IL-18 (38.16±17.02 pg/ml)and TNF-α(42.68±11.18 pg/ml)were obviously higher than those in the other two groups (t=4.35~20.43,P value<0.001),and the level of IL-10 (8.62±2.98 pg/ml)and SOD (95.36±20.03 μmol/L) was lower than those in the other two groups (t=3.67~23.74,P value<0.001).Correlation analysis found that MDA of Uu+ infertility group was positively correlated with TNF-α,IL-18 (r=0.61,0.55,P value<0.001),and negatively correla-ted with SOD and IL-10 (r=-0.55,-0.53,P value<0.001).Conclusion The results suggested that Uu infection caused the level of reactive oxidative increasing,cytokines counterbalance disorder and affected sperm quality.So it is of great signif-icance for the treatment to test the levels of ROS and cytokines in patients with male sterility.

To investigate the effects of gambognic acid (GA) on TRAIL-induced apoptosis of cancer cells, human colon HT-29 cancer cells were treated with GA to promote apoptosis. Inhibition of the cell proliferation was measured with MTT assay and cell apoptosis was detected with formation of DNA ladders in agarose gel electrophoresis, and activation of caspase activity. The content of cytosolic reactive oxygen species (ROS) was measured with flow cytometry. The activities of Caspase-3, -8, -9 were detected using spectrophotometric assay. The levels of c-FLIP, CHOP, DR4 and DR5 in cells were tested by Western blot. Combination of GA (1 µg · mL(-1)) and TRAIL (40 ng · mL(-1)) significantly reduced proliferation and increased apoptosis of HT-29 cells over those induced by each agent alone. Percentage of apoptotic cells was increased to 45.5%. GA markedly enhanced the intracellular ROS generation. Expression of CHOP, DR4 and DR5 was up-regulated to 7.38, 5.41, and 4.85 times of the control group, respectively. GA promoted activation of Caspase-3, -8, and -9 by TRAIL (P<0.05). Furthermore, the expression of anti-apoptotic protein c-FLIP was down-regulated to 0.22 ± 0.08 times of the control group. In conclusion, GA sensitizes HT-29 cells to TRAIL-induced apoptosis by promoting ROS-activated ERS pathways, up-regulating of DR4 and DR5, and inhibiting c-FLIP expression.

Purpose To identify whether serum-free culture can enrich breast cancer stem cells from MCF-7 human breast cancer cell line. Methods MCF-7 human breast cancer cell line by serum-free culture and serum culture technology were cultured, its cell mor-phology and growth pattern were observed by the inverted microscope. The expression of stem cell surface molecular makers CD24, CD44 was observed by the inverted fluorescence microscope and the flow cytometry, the proportion of different subpopulation cells was detected by the flow cytometry. At the same time, difference of the cell cycle was detected by the flow cytometry. Results The cell line cultured by serum-free culture grew in the form of suspended microspheres of different sizes in the medium, but the cell line cul-tured by serum culture grew in the form of monolayer adherent growth. There was no obvious difference in the expression of stem cell surface molecular makers CD44 between the suspended microsphere cells and the adherent cells, but the expression of CD24 in the sus-pended microsphere cells decreased compared to the adherent cells. The proportion of CD44 + /CD24 -/low phenotype cells in the suspen-ded microsphere cells and the adherent cells was (86. 93 ± 0. 53)% and (19. 98 ± 0. 62)%, respectively (P<0. 05), the proportion of CD44 + /CD24 + phenotype cells was (12. 68 ± 0. 59)% and (79. 90 ± 0. 57)%, respectively (P<0. 05). The proportion of mitotic cells in the suspended microsphere cells and the adherent cells was ( 18. 85 ± 2. 26 )% and ( 43. 91 ± 1. 81 )%, respectively ( P<0. 05), the proportion of quiescent cells was (64. 92 ± 2. 07)% and (39. 82 ± 1. 77)%, respectively (P<0. 05). Conclusion CD44 + /CD24 -/low breast cancer stem cells can be effectively enriched by the serum-free culture technology.