CMIR: A Unified Cross-Modality Framework for Preoperative Accurate Prediction of Microvascular Invasion in Hepatocellular Carcinoma.

Microvascular invasion of HCC is an important factor affecting postoperative recurrence and prognosis of patients. Preoperative diagnosis of MVI is greatly significant to improve the prognosis of HCC. Currently, the diagnosis of MVI is mainly based on the histopathological examination after surgery, which is difficult to meet the requirement of preoperative diagnosis. Also, the sensitivity, specificity and accuracy of MVI diagnosis based on a single imaging feature are low. In this paper, a robust, high-precision cross-modality unified framework for clinical diagnosis is proposed for the prediction of microvascular invasion of hepatocellular carcinoma. It can effectively extract, fuse and locate multi-phase MR Images and clinical data, enrich the semantic context, and comprehensively improve the prediction indicators in different hospitals. The state-of-the-art performance of the approach was validated on a dataset of HCC patients with confirmed pathological types. Moreover, CMIR provides a possible solution for related multimodality tasks in the medical field.

MVI-Wise GAN: Synthetic MRI to Improve Microvascular Invasion Prediction in Hepatocellular Carcinoma.

MRI is crucial for the diagnosis of HCC patients, especially when combined with CT images for MVI prediction, richer complementary information can be learned. Many studies have shown that whether hepatocellular carcinoma is accompanied by vascular invasion can be evidenced by imaging examinations such as CT or MR, so they can be used as a multimodal joint prediction to improve the prediction accuracy of MVI. However, it is high-risk, time-consuming and expensive in current clinical diagnosis due to the use of gadolinium-based contrast agent (CA) injection. If MRI could be synthesized without CA injection, there is no doubt that it would greatly optimize the diagnosis. Based on this, this paper proposes a high-quality image synthesis network, MVI-Wise GAN, that can be used to improve the prediction of microvascular invasion in HCC. It starts from the underlying imaging perspective, introduces K-space and feature-level constraints, and combines three related networks (an attention-aware generator, a convolutional neural network-based discriminator and a region-based convolutional neural network detector) Together, precise tumor region detection by synthetic tumor-specific MRI. Accurate MRI synthesis is achieved through backpropagation, the feature representation and context learning of HCC MVI are enhanced, and the performance of loss convergence is improved through residual learning. The model was tested on a dataset of 256 subjects from Run Run Shaw Hospital of Zhejiang University. Experimental results and quantitative evaluation show that MVI-Wise GAN achieves high-quality MRI synthesis with a tumor detection accuracy of 92.3%, which is helpful for the clinical diagnosis of liver tumor MVI.

Vision-Guided Attention-Enhanced Network for Predicting Microvascular Invasion in Hepatocellular Carcinoma.

As the most common malignant tumor worldwide, hepatocellular carcinoma (HCC) has a high rate of death and recurrence, and microvascular invasion (MVI) is considered to be an independent risk factor affecting its early recurrence and poor survival rate. Accurate preoperative prediction of MVI is of great significance for the formulation of individualized treatment plans and long-term prognosis assessment for HCC patients. However, as the mechanism of MVI is still unclear, existing studies use deep learning methods to directly train CT or MR images, with limited predictive performance and lack of explanation. We map the pathological "7-point" baseline sampling method used to confirm the diagnosis of MVI onto MR images, propose a vision-guided attention-enhanced network to improve the prediction performance of MVI, and validate the prediction on the corresponding pathological images reliability of the results. Specifically, we design a learnable online class activation map (CAM) to guide the network to focus on high-incidence regions of MVI guided by an extended tumor mask. Further, an attention-enhanced module is proposed to force the network to learn image regions that can explain the MVI results. The generated attention maps capture long-distance dependencies and can be used as spatial priors for MVI to promote the learning of vision-guided module. The experimental results on the constructed multi-center dataset show that the proposed algorithm achieves the state-of-the-art compared to other models.

Elucidation of Geniposide and Crocin Accumulation and Their Biosysnthsis-Related Key Enzymes during Gardenia jasminoides Fruit Growth.

Gardenia jasminoides fruits are extensively grown worldwide, with a large harvest, and its major medicinal ingredients are geniposide and crocins. Research on their accumulation and biosynthsis-related enzymes is rare. In this study, the accumulation of geniposide and crocin of G. jasminoides fruits at different developmental stages were clarified by HPLC. The highest cumulative amount of geniposide was 2.035% during the unripe-fruit period, and the highest content of crocin was 1.098% during the mature-fruit period. Furthermore, transcriptome sequencing was performed. A total of 50 unigenes encoding 4 key enzymes related in geniposide biosynthsis pathways were screened, and 41 unigenes encoding 7 key enzymes in the pathways of crocin were elucidated. It was found that the expression levels of differentially expressed genes of DN67890_c0_g1_i2-encoding GGPS, which is highly related to geniposide biosynthesis, and DN81253_c0_g1_i1-encoding lcyB, DN79477_c0_g1_i2-encoding lcyE, and DN84975_c1_g7_i11-encoding CCD, which are highly related to crocin biosynthesis, were consistent with the accumulation of geniposide and crocin content, respectively. The qRT-PCR results showed that the trends of relative expression were consistent with transcribed genes. This study provides insights for understanding the geniposide and crocin accumulation and biosynthsis during fruit development in G. jasminoides.

Brain Inflammatory Marker Abnormalities in Major Psychiatric Diseases: a Systematic Review of Postmortem Brain Studies.

Schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) are common neuropsychiatric disorders that lead to neuroinflammation in the pathogenesis. It is possible to further explore the connection between inflammation in the brain and SCZ, BD, and MDD. Therefore, we systematically reviewed PubMed and Web of Science on brain inflammatory markers measured in SCZ, BD, and MDD postmortem brains. Out of 2166 studies yielded by the search, 46 studies met the inclusion criteria in SCZ, BD, and MDD postmortem brains. The results were variable across inflammatory markers. For example, 26 studies were included to measure the differential expression between SCZ and control subjects. Similarly, seven of the included studies measured the differential expression of inflammatory markers in patients with BD. The heterogeneity from the included studies is not clear at present, which may be caused by several factors, including the measured brain region, disease stage, brain source, medication, and other factors.

The antifibrotic effects of the novel compound gorse isoflavone alkaloid on chemical liver injury in rats.

OBJECTIVE: Liver fibrosis is a frequently occurring liver injury which lacks of effective treatment clinically. Here, we investigated the protective effects of a novel compound Gorse isoflavone alkaloid (GIA) against liver fibrosis. METHODS: Totally forty rats were randomly divided into four groups. Then we established a model of liver fibrosis induced by the intragastric administration of carbon tetrachloride (CCl4). This treated group was followed by the intragastric administration of GIA and colchicine. Then the liver index and spleen index, and liver function indexes were detected by kit. Western blotting assay was performed to estimate the expression of Transforming Growth Factor-ß1 (TGF-ß1) and related proteins. Tissue fibrosis was observed by Masson staining. RESULTS: Our results suggested that GIA reduced the deposition of collagen fibres and the fibrosis index hydroxyproline (Hyp) of liver tissue. Furthermore, we found that GIA significantly decreased the expression of Transforming Growth Factor-ß1 (TGF-ß1) and the ratio of p-smad2/3 to smad2/3, enhanced the level of superoxide dismutase (SOD), and decreased the concentration of malonic dialdehyde (MDA) in the liver. CONCLUSIONS: Our findings revealed that GIA has a beneficial effect to resist the liver fibrosis, and could be ideal for potential use in antifibrotic drugs for the liver.

Residual Multilayer Perceptrons for Genotype-Guided Recurrence Prediction of Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is a malignant tumor with high morbidity and mortality, with a high recurrence rate after surgery, which directly affects the life and health of patients. Recently, many studies are based on Computed Tomography (CT) images. They are cheap but have low accuracy. In contrast, the use of gene expression data to predict the recurrence of NSCLC has high accuracy. However, the acquisition of gene data is expensive and invasive, and cannot meet the recurrence prediction requirement of all patients. In this paper, we proposed a low-cost, high-accuracy residual multilayer perceptrons (ResMLP) recurrence prediction method. First, several proposed ResMLP modules are applied to construct a deep regression estimation model. Then, we build a mapping function of mixed features (handcrafted features and deep features) and gene data via this model. Finally, the recurrence prediction task is realized, by utilizing the gene estimation data obtained from the regression model to learn the information representation related to recurrence. The experimental results show that the proposed method has strong generalization ability and can reach 86.38% prediction accuracy. Clinical Relevance- This study improved the preoperative recurrence of NSCLC prediction accuracy from 78.61% by the conventional method to 86.38% by our proposed method using only the CT image.

MiR-126-5p Promotes Tumor Cell Proliferation, Metastasis and Invasion by Targeting TDO2 in Hepatocellular Carcinoma.

TDO2 is a key enzyme in the kynurenine metabolic pathway, which is the most important pathway of tryptophan metabolism. It has been shown that miRNAs are involved in cell metastasis through interaction with target mRNAs. In this study, we found 645 miRNAs that could be immunoprecipitated with TDO2 through the RNA-immunoprecipitation experiment. miR-126-5p was selected as the research target, which was also confirmed by dual-luciferase reporter assay. Through qRT-PCR analysis, it was verified that the overexpression of miR-126-5p promoted the expression of TDO2, PI3K/AKT and WNT1. Meanwhile, it was verified that overexpression of miR-126-5p can promote intracellular tryptophan metabolism by HPLC. We also verified the effects of miR-126-5p on cell proliferation, migration, and invasion by cck-8, cell colony formation and trans-well assay in both HCCLM3 cells and HepG2 cells. In vivo experiments were also conducted to verify that miR-126-5p promoted tumor formation and growth via immunohistochemical detection of cell infiltration and proliferation to generate markers Ki-67, BAX, and VEGF. In conclusion, our results suggest that miR-126-5p is a biomarker and a potential new treatment target in the progression of HCC via promoting the expression of TDO2.

Changes in the hepatic differentiation potential of human mesenchymal stem cells aged in vitro.

BACKGROUND: Due to their multipotency and ability for self-renewal, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold great promise for generating hepatocytes. Previous research has successfully generated hepatocytes from early-passage [i.e., passage (P)3] hUC-MSCs; however, the populations of early-passage cells are limited, and these cells cannot produce sufficient functional hepatocytes for large-scale application in clinical therapy. Thus, a thorough investigation of the hepatic differentiation potential of in vitro-aged hUC-MSCs is needed. METHODS: hUC-MSCs were passaged in vitro and subcultured every 3 days up to P8, and their morphology, proliferative capacity, liver-specific marker expression, and liver function at the end of each passage were analyzed. The efficiency of the hepatogenic differentiation of hUC-MSCs driven by a functional hit 1 (FH1)-based strategy at different passages was also evaluated. RESULTS: The in vitro-aged hUC-MSCs gradually displayed morphological inhomogeneity, had reduced proliferative capability, and exhibited senescent properties while maintaining adipogenic and osteogenic differentiation potential. Additionally, senescence also decreased the expression of messenger RNA (mRNA) levels in albumin (ALB) and alpha 1-antitrpsin (A1AT) in these cells and their relative protein expression, which is the marker of a mature hepatocyte. The liver function of the in vitro-aged hUC-MSCs also deteriorated gradually. Finally, the percentage of hepatocyte-like cells (HLCs) generated from in vitro-aged hUC-MSCs reduced significantly, and the mature hepatocyte functions, such as ALB secretion, glycogen synthesis, low-density lipoprotein (LDL) intake, and indocyanine green (ICG) uptake, also changed. CONCLUSIONS: hUC-MSCs possess mature hepatocytes' specific markers and functions, which change gradually as they undergo cell senescence. Due to the loss of these properties within in vitro subcultures, the hepatic differentiation efficiency of in vitro-aged hUC-MSCs decreased dramatically in the late passage (P8). The current study provides valuable information can inform future research on liver disease.

Tryptophan Side-Chain Oxidase Enzyme Suppresses Hepatocellular Carcinoma Growth through Degradation of Tryptophan.

Tryptophan metabolism plays a role in the occurrence and development of hepatocellular carcinoma cells. By degrading certain amino acids, tumor growth can be limited while maintaining the body's normal nutritional requirements. Tryptophan side-chain oxidase (TSO) enzyme can degrade tryptophan, and its inhibitory effect on hepatocellular carcinoma cells is worthy of further study. To investigate the degradation effect on tryptophan, TSO was isolated and purified from qq Pseudomonas. The reaction products were identified with high performance liquid chromatography (HPLC) and high-performance liquid chromatography tandem mass spectrometry (HPLC-MS). De novo sequencing provided the complete amino acid sequence of TSO. The results of CCK-8, colony formation, transwell, and qPCR confirmed that TSO had inhibitory effects on the proliferation and migration of HCCLM3 (human hepatocarcinoma cell line) and HepG2 cells. The results of flow cytometry confirmed its apoptotic activity. In animal experiments, we found that the tumor-suppressive effect was better in the oncotherapy group than the intraperitoneal injection group. The results of immunohistochemistry also suggested that TSO could inhibit proliferation and promote apoptosis. In conclusion, a specific enzyme that can degrade tryptophan and inhibit the growth of hepatoma cells was authenticated, and its basic information was obtained by extraction/purification and amino acid sequencing.

Functional hit 1 (FH1)-based rapid and efficient generation of functional hepatocytes from human mesenchymal stem cells: a novel strategy for hepatic differentiation.

BACKGROUND: Because the liver is central to the physiology of the body, primary hepatocytes are widely used in liver pathology and physiological research, such as liver drug screening, bioartificial liver support system, and cell therapy for liver diseases. However, the source of primary hepatocytes is limited. We describe a novel non-transgenic protocol that facilitates the rapid generation of hepatocyte-like cells from human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), providing a new source of functional hepatocytes. METHODS: In this study, we used hUC-MSCs and human induced pluripotent cells (iPSCs) derived mesenchymal stem cells (iMSCs) to investigate the new induction strategy. Passage 3 MSCs were induced into hepatocyte-like cells using small-molecule compounds combined with cell factors in vitro. Functional hit 1 (FH1), a promising small molecule compound was achieved to replace HGF in the hepatocyte maturation stage to induce the hepatocyte-like cells differentiation. RESULTS: We rapidly induced hUC-MSCs and human iMSCs into hepatocyte-like cells within 10 days in vitro, and the cells were morphologically similarly to both hepatocytes derived from the hepatocyte growth factor (HGF)-based method and the primary hepatocytes. They expressed mature hepatocyte special genes and achieved functions such as glycogen storage, albumin expression, urea secretion, cytochrome P450 activity, Low-density lipoprotein (LDL) uptake, and indocyanine green (ICG) uptake. CONCLUSIONS: We successfully established a small-molecule protocol without using HGF to differentiate MSCs into hepatocyte-like cells, which provides a rapid and cost-effective platform for in vitro studies of liver disease.

Safety assessment of subtilisin QK in rats.

BACKGROUND: Subtilisin QK is a serine protease in the subtilisin family, and is fermented by Bacillus subtilis QK02. The fibrinolytic activity of subtilisin QK was measured by detecting low molecular weight degradation products using a spectrophotometric method developed by Japan Bio Science Laboratory Co., Ltd. Subtilisin QK powder can maintain its fibrinolytic activity for more than 24 months when it is stored at room temperature and protected from light. Our previous results showed that subtlisin QK directly degraded cross-linked fibrins in the fibrin plate assay and effectively inhibited thrombosis in the mouse thrombus model. The aim of this study was to determine the acute toxicity, potential subchronic toxicity, and safety pharmacology of subtilisin QK in Sprague-Dawley (SD) rats. METHODS: In the acute toxicity study, a single oral dose of 100,000 FU/kg was administered to 10 female and 10 male SD rats. In the 28-day subchronic toxicity, 60 female and 60 male SD rats were randomly assigned to four experimental groups (daily oral dose of 0, 2500, 7500 and 25,000 FU/kg). In the safety pharmacology study, 20 female and 20 male SD rats were randomly assigned to four experimental groups (single oral dose of 0, 500, 1500 and 5000 FU/kg). RESULTS: No death occurred and no adverse effects were observed in the acute toxicity study at a dose of 100,000 FU/kg. In the 28-day subchronic toxicity study, several hematological and blood biochemical parameters showed increases or decreases; however, due to the lack of a dose-response relationship, these differences were considered unrelated to treatment. In the safety pharmacology study, no adverse effects were observed on the central nervous of SD rats post-administration up to a dose of 5000 FU/kg subtilisin QK. CONCLUSION: The results showed that oral consumption of subtilisin QK is of low toxicological concern. No adverse effects were observed at doses of 2500, 7500, and 25,000 FU/kg in the 28-day subchronic toxicity, and the no-observed-adverse-effect level (NOAEL) of subtilisin QK was 25,000 FU/kg.

Traditional Chinese Medicine Decoction Combined With Antipsychotic for Chronic Schizophrenia Treatment: A Systematic Review and Meta-analysis.

Despite several studies suggesting the effectiveness of traditional Chinese medicine (TCM) in schizophrenia, there is still a lack of systematic summary and analysis on the role of TCM as adjuvant therapy in chronic schizophrenia. For this purpose, we conducted a meta-analysis to study the efficacy of TCM as an adjuvant combined with antipsychotics in the treatment of chronic schizophrenia. Until April 2020, based on the review of six electronic databases, eight articles were selected. The articles compared TCM decoction assisted antipsychotic therapies with an antipsychotic alone in the treatment of chronic schizophrenia by analyzing a total of 810 cases. The results showed that TCM combined with antipsychotics have beneficial effects on the Positive and Negative Syndrome Scale (PANSS), including the changes in total score, negative score, and the clinical effects evaluated by the PANSS scale. Subgroup analysis showed that the effects of auxiliary TCM with different efficacy on the positive and psychopathological scores were significantly different. It was found that adjuvant treatment with TCM can reduce some side effects and improve the patient's living conditions in the evaluation of the Schizophrenia Quality Of Life Scale (SQLS). Many studies have proved that TCM is safe and well-tolerated. Although the difficulties of using limited TCM remains to be generalized, it still has great potential in the adjuvant treatment of chronic schizophrenia.

Clinical observation on therapeutic effect of Huangqi granules combined with external therapy in treatment of stress injury / 中国中西医结合急救杂志

Objective To observe the effect of Huangqi granules combined with external treatment on the clinical therapeutic effects of typeⅡand Ⅲ stress injuries. Methods A total of 240 patients with typeⅡ andⅢ pressure injuries admitted to the Hengshui People's Hospital from January 2017 to March 2019 were enrolled. According to difference in therapeutic methods, the patients were divided into astragalus mongholicus granule group and routine treatment of Western medicine group, with 120 cases in each group. In both groups, the patients were given routine nursing treatment such as air cushion bed, regular body turn-over, nutrition support, health education, etc;in routine Western medicine treatment group, according to the principle of aseptic dressing change, the wounds were treated and covered with foam dressing; while in the astragalus mongholicus granule group, the routine nursing care and sterile dressing as above mentioned were also applied, additionally 3 bags of oral astragalus mongholicus granules mixed with boiled water each time, twice a day (equivalent to 10 g for each bag of Chinese herbal slices), 7 days as one course of treatment; at the same time, the wound was sterilized, debrided and washed with normal saline, and after drying, the rubber Shengji ointment for promoting growth of tissue was evenly spread on the wound and covered with foam dressing. In the two groups, the changes of pressure ulcer healing evaluation scale (PUSH) scores before treatment and 7, 14, 21 and 28 days after treatment, as well as the differences in wound healing time and clinical efficacy between the two groups after treatment were observed, and the recurrence rate was followed up for 10 weeks. Results Compared with routine Western medicine group, the Ⅱand Ⅲ wound healing times were significantly reduced in the astragalus mongholicus granule group [the days of wound healing for Ⅱ stress injury (days): 7.81±1.40 vs. 16.52±1.89, the days of wound healing for Ⅲ stress injury (days): 14.60±1.50 vs. 20.23±1.27, both P < 0.05]. With the prolongation of therapeutic time, the PUSH scores of two groups decreased gradually, there was no significant difference in the PUSH scores between the two groups before treatment and 7 days after treatment (both P > 0.05); after 14 days of treatment, the PUSH score of astragalus mongholicus granule group was significantly lower than that of the routine western medicine group (7.82±1.93 vs. 9.96±1.89), and lasted until 28 days (4.16±0.47 vs. 5.29±0.57), the differences being statistically significant (both P < 0.05). The total effective rate of the astragalus mongholicus granule group was significantly higher than that of the routine western medicine treatment group [99.41% (171/172) vs. 74.51% (114/153), P < 0.05], and the recurrence rate of the mongholicus granule group was obviously lower than the routine Western medicine treatment [3.60% (5/139) vs. 17.74% (11/62), P < 0.05]. Conclusion Oral astragalus mongholicus granules combined with myocreatic ointment external therapy can effectively shorten the healing time of type Ⅱand Ⅲ stress injury, improve the cure rate and reduce the recurrence rate.

Influences of dissolved humic acid on Zn bioavailability and its consequences for thyroid toxicity.

This study aimed to investigate the effect of dissolved humic acid (dHA) on Zn bioavailability and the subsequent influence on the Zn-induced thyroid toxicity. Zn toxicity was assessed using a yeast bioassay in the presence and absence of dHA. With increasing concentration of dHA, the toxic effects decreased, and the free Zn concentrations detected by the anodic stripping voltammetry (ASV) method also decreased. The high correlation (R = 0.92, p < 0.001) between toxic effects and free Zn concentrations indicated that Zn thyroid toxicity largely comes from the free Zn fraction. Water samples from the Qing River in Beijing were also assayed for thyroid toxicity. The results revealed that the metals might contribute to the toxicity. The known thyroid hormone-disrupting metals, namely, Zn, Cd and Hg, were analyzed. The cause-effect relationship between the observed thyroid toxicity and free Zn concentrations as well as their dose-effect relationships were examined. Our results showed that Zn might be the major contributor to the observed thyroid toxicity caused by metals. These results suggest that the ASV method and the identified major contributor (Zn) may be used in lieu of conventional environmental analyses to follow the progression of a risk assessment or remediation strategy.

Effects of Modified Qianjin Weijing Decoction on TNF-α and NF-κB in Rats with Lung Injury Induced by Particulate Matter / 中国中医药信息杂志

Objective To investigate the protective effect of modified Qianjin Weijing Decoction(MQJWJD)on TNF-α and NF-κB in rats with lung injury induced by particulate matter; To discuss relevant mechanism of action. Methods A tracheal drip 15 mg/kg fine particles of saline solution was used to establish modeling, every other day, three times. Thirty-two Wistar rats were randomly divided into normal group, model group and MQJWJD high-dose and low-dose groups, with eight rats in each group. Medication groups were given relevant medicine for gavage. The level of TNF-α in bronchoalveolar lavage fluid (BALF) was measured by ELISA. The expression of NF-κB protein in lung tissues was measured by immunohistochemistry. The histopathology of the lung injury was observed by light microscope. Results Compared with normal group, the level of TNF-α and the expression of NF-κB protein in the model group were higher than those in the normal group (P<0.01). Compared with model group, the level of TNF-α and the expression of NF-κB protein in MQJWJD low-dose and high-dose groups were lower than those in the model group (P<0.05, P<0.01). Pathological observation showed that, compared with normal group, model group showed intratracheal, alveolar and interstitial bacteria within a large number of fine particles calm, alveolar and pulmonary interstitial visible large amounts of phagocytic fine particles of macrophages and accompanied by more neutrophils and lymphocyte infiltration; Lung tissue pathological changes were significantly lighter in MQJWJD high-dose and low-dose groups than the model group. MQJWJD high-dose group showed mild inflammation, alveolar and pulmonary interstitial visible phagocytic fine particles of macrophages, a small amount of neutrophils and lymphocyte infiltration. Conclusion MQJWJD can reduce the pulmonary injury in rats induced by particulate matter and has protective effects on the rat model through decreasing the levels of TNF-α and the expressions of NF-κB protein in injured lung tissues.

Effect of sucralfate on cytokines in rat with paraquat poisoning / 中华危重病急救医学

Objective To explore the effect of sucralfate on cytokines in rats with paraquat (PQ) poisoning. Methods Seventy-two healthy male Sprague-Dawley (SD) rats were randomly divided into PQ model group, sodium bicarbonate intervention group (SB group) and sucralfate suspension gel group (LTL group), with 24 rats in each group. The rat model of PQ poisoning was reproduced by one-time intragastric administration of PQ solution 25 mg/kg. The rats in SB group and LTL group were intragastricly administrated with 5 mL·kg-1·d-1of 100 g/L sodium bicarbonate or 200 g/L sucralfate at 2 hours after exposing to PQ, and the rats in PQ model group were given the same amount of sterile saline. The abdominal aortic blood of rats was collected at 1, 3, 6, and 10 days after PQ poisoning, and the levels of serum tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) were determined by enzyme-linked immunosorbent assay (ELISA). The left lung tissue was harvested, and lung wet/dry weight (W/D) ratio was assessed. Results With prolonged exposure, lung W/D ratios in all the groups were increased gradually, reached the peak at 10 days, but in the SB group and LTL group, the amplitude of increase was obviously reduced, the ratios were significantly decreased at 6 days and 10 days as compared with those in PQ model group (SB group vs. PQ model group: 4.99±0.79 vs. 6.98±0.86 at 6 days, 5.61±0.36 vs. 7.36±0.95 at 10 days; LTL group vs. PQ model group: 4.61±0.24 vs. 6.98±0.86 at 6 days, 4.24±0.20 vs. 7.36±0.95 at 10 days, all P < 0.05), but there was no significant difference between SB group and LTL group (all P > 0.05). After PQ poisoning, the levels of TNF-α, IL-10 and TGF-β1 were elevated, and reached the peak at 3 days and then decreased gradually. Compared with the PQ model group, serum TNF-α, IL-10 and TGF-β1 levels in SB group and LTL group were decreased significantly [SB group vs. PQ model group: 3-day TNF-α (ng/L) was 147.6±12.3 vs. 168.2±11.3, 3-day IL-10 (ng/L) was 65.4±3.2 vs. 115.1±9.2, 3-day TGF-β1 (ng/L) was 356.3±50.3 vs. 415.6±68.3; LTL group vs. PQ model group: 3-day TNF-α (ng/L) was 82.2±7.4 vs. 168.2±11.3, 3-day IL-10 (ng/L) was 44.4±5.2 vs.115.1±9.2, 3-day TGF-β1 (ng/L) was 296.3±40.2 vs. 415.6±68.3, all P < 0.05], especially in LTL group (all P < 0.05). Conclusion Early gastrointestinal lavage with sucralfate could effectively reduce the inflammatory exudation in lung tissue after PQ poisoning, and inhibit the cytokine secretion.

Experimental study of sucralfate intervention for paraquat poisoning in rats.

OBJECTIVE: This study explored the effects of sucralfate intervention as a novel treatment for paraquat (PQ) poisoning in Sprague-Dawley (SD) rats. METHODS: After PQ poisoning, the SD rats were randomly divided into the PQ control group (treated with normal saline), the sodium bicarbonate (SB) treatment group, and the sucralfate (LTL) treatment group. Then, the rats were administered normal saline, sodium bicarbonate solution, or sucralfate suspension as an intervention by gastric lavage. At 1, 3, 6, and 10days after poisoning, the left lungs of some rats were removed to determine the lung wet/dry (W/D) weight ratio. Additionally, the serum cytokine levels were measured, and the lung and kidney tissues were pathologically examined. RESULTS: After treatment, the signs and symptoms of the rats were improved, the mortality rate was reduced, the W/D weight ratio of the lung was lower, the cytokine levels [transforming growth factor (TGF)-ß1, interleukin (IL)-10, and tumor necrosis factor (TNF)-α] were decreased, and the pathological injuries of the lungs and kidneys were improved. Moreover, sucralfate was significantly more effective than the control (normal saline) group and the SB treatment group. CONCLUSION: The results showed that early gastrointestinal lavage with sucralfate effectively reduced the inflammatory response and lung and kidney injuries and improved the survival of the SD rats.

[Effect of Dissolved Humic Acid on Thyroid Receptor Antagonistic Activity of Zinc in Aquatic Environment].

A rapid recombinant human thyroid (hTR) gene yeast bioassay was used to evaluate the effect of dissolved humic acid on thyroid receptor antagonistic activity of ZnCl2.The concentration of bio-available zinc after its reaction with dissolved humic acids was measured by anodic stripping voltammetry (ASV).Furthermore,the reaction mechanism of humic acid and zinc was investigated by three-dimensional excitation-emission matrix fluorescence spectroscopy (3DEEM).The results revealed that ZnCl2 demonstrated strong thyroid receptor antagonistic activity,and the concentration inhibiting 20% of the maximum effect of ZnCl2 was 1.70×10-5 mol·L-1.The thyroid receptor antagonistic activity of ZnCl2 was reduced by 30%-50% after the reaction of dissolved humic acids.The results of ASV showed that the concentration of bio-available zinc was decreased after the reaction of dissolved humic acids,the result was similar to that of bioassay test.The thyroid receptor antagonistic activity of the mixed solution of humic acid and ZnCl2 was increased after UV radiation treatment,however it was still lower than the antagonistic activity induced by ZnCl2.The results of 3DEEM showed that ZnCl2 could reduce the fluorescence peak intensity of humic acid,which could intuitively characterize the interaction between humic acid and ZnCl2.The above results can provide basic data and theoretical support for zinc toxicity study in aquatic environment and the establishment of water quality criteria for znic.

Epidemiology and clinical characteristics of type 1 autoimmune pancreatitis / 基础医学与临床

Objective To improve the diagnosis and treatment of type Ⅰ autoimmune pancreatitis, a study was carried out to summarize the epidemiological characteristics, clinical manifestations and diagnosis of autoimmune pancreatitis (AIP).Methods This study retrospectively analyzed the clinical data of all the patients diagnosed with AIP from January 1998 to December 2016 in the ward of Peking union medical college hospital.Results 194 type 1 AIP patients were enrolled in this study.The M/F ratio of the disease was 3.51/1,with an average age of 57±15 years.The most common symptom is jaundice, abdominal pain and weight loss.The most common diseases of the pancreas are sclerosing cholangitis, salivary glands, IgG4 nephropathy.There are 36.68 percent of AIP patients with diabetes mellitus.IgG4, ANA, ESR, c-reactive protein and CA199 are all contribute to disease diagnosis and follow-up.Pathology, pet-CT and hormone therapy response all contribute to the diagnosis of AIP.Conclusions As a systemic disease, the type 1 AIP has special clinical features and laboratory profiles.The diagnosis of AIP can be applied in many ways.