Impact of particulate matter 2.5 on the liver function of mice.

OBJECTIVE: The aim of this study was to evaluate the impact of particulate matter 2.5 (PM2.5) on liver function at the animal level and to study its impact targets. MATERIALS AND METHODS: 60 male and female BALB/c mice of SPF grade, aged 6-8 weeks, were randomly divided into four groups, with 15 mice in each, including the normal saline control group, the PM2.5 low dose group [2 µg/(100 g/d)], the PM2.5 medium dose group [8 µg/(100 g/d)] and the PM2.5 high dose group [16 µg/(100 g/d)]. Each day, 0.9% saline or PM2.5 particles were administered through the nasal route, and samples were taken after 3 weeks of continuous exposure. Hematoxylin-eosin staining (HE) was used to observe the liver damage caused by PM2.5. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected by using an automatic biochemical analyzer to detect the content of liver glycogen and blood glucose. Multiple indicators were observed, including plasma tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) levels, oxidative stress response indicators reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) detection, RT-PCR and Western blot detection of glycogen synthase (GS), glucokinase (GK), nuclear factor erythroid 2-related factor 2 (Nrf2) expression and phosphorylation level of phospho-c-Jun N-terminal kinases (p-JNK). RESULTS: PM2.5 can cause damage to the liver by increasing PM2.5 concentrations, raising the metabolic rate of liver cells, resulting in a substantial amount of inflammatory infiltration and vacuolar degeneration of cells, and increasing the liver/body weight. TNF-α and IL-6 inflammatory factor expression increased (p<0.05). An increase in the serum ALT and AST levels were also observed. The blood glucose of mice increased, whereas the content of liver glycogen declined (p<0.05). ROS, MDA, and SOD levels all increased considerably. PM2.5 can drastically lower the expression of GS and GK, increase the expression of Nrf2, and raise the phosphorylation level of p-JNK (p<0.05). CONCLUSIONS: PM2.5 can induce oxidative stress in mouse liver through the Nrf2/JNK pathway, induce liver inflammation in mice, and inhibit glycogen synthesis.

[Intravenous infusion of methylene blue to visualize the ureter in laparoscopic colorectal surgery].

Objective: Intraoperative localization of the ureter can contribute to accurate dissection and minimize ureteral injury in colorectal surgery. We aim to summarize a single center's experience of fluorescence ureteral visualization using methylene blue (MB) and explore its visualization efficiency. Methods: This is a descriptive case-series-study. Clinical data of patients who had undergone laparoscopic colorectal surgery and fluorescence visualization of the ureter in the Gastrointestinal Surgery Department of Guangdong Provincial People's Hospital from March 2022 to May 2022 were retrospectively collected. Patients with incomplete surgery videos, renal insufficiency, or allergic reactions were excluded. MB was infused with 0.9% NaCl at 1.0 mg/kg in 100 mL of normal saline for 5 to 15 minutes during laparoscopic exploration. Imaging was performed using a device developed in-house by OptoMedic (Guangdong, China) that operates at 660nm to achieve excitation of MB. Clinical information, MB dosage, rate of successful fluorescence, time to fluorescence, operation time, blood loss, intraoperative blood oxygen levels, pathological staging, changes in renal function, and post-operative complications were retrospectively analyzed. Results: The study cohort comprised 27 patients (24 men and 3 women) with an average age of (60.25±16.95) years and an average body mass index of (21.72±3.42) kg/m2. The dosage of MB was 0.3-1.0 mg/kg and the infusion time was 5-15 minutes. Fluorescence signals were detected in all patients. The median time to signal detection was 20 (range, 10 to 40) minutes after MB infusion. The range of intraoperative blood oxygen fluctuation averaged 2.5% (range, 0 to 7.0%). The median change in creatine concentration was -1.3 (range, -17.2 to 29.2) µmol/L. No patients had complications associated with use of MB. Fluorescence visualization of the ureter was very valuable clinically in two patients (thick mesentery, stage T4). Conclusion: MB is a safe and effective means of visualizing the ureter by fluorescence during laparoscopic colorectal surgery, especially when the procedure is difficult. MB in a dosage of less than 1 mg/kg can slowly infused for more than 5 minutes during laparoscopic exploration. During the infusion, attention must be paid to blood oxygen fluctuations.

[Bipolar androgen therapy followed by immune checkpoint inhibitors in metastatic castration resistant prostate cancer: A report of 4 cases].

The relationship between androgen and prostate cancer treatment has plagued the field of urologic oncology. To investigate the efficacy and safety of bipolar androgen therapy (BAT) followed by immune checkpoint inhibitor therapy in patients with metastatic castration resistant prostate cancer (mCRPC). In August 2020, Beijing Hospital conducted an investigator-initiated study: Bipolar androgen therapy followed by immune checkpoint inhibitor therapy in metastatic castration resistant prostate cancer. Up to now, the study has included 4 patients who completed the entire cycle of treatment. The mean age of the patients was 74.5 (68 to 82) years old, the mean prostate-specific antigen (PSA) was 20.8 (9.9 to 8.36) µg/L, the mean testosterone was 0.50 (0.00 to 1.81) µg/L, and the Gleason score were 10 and 9, 7, 7 respectively. The pain scale score before treatment was 1.5 (1 to 2). In this study, 4 patients completed the entire cycle of treatment, and the treatment effect of the patients showed great heterogeneity. PSA in case 1 decreased from 24.0 µg/L to 0.47 µg/L, testosterone increased from 0.175 6 µg/L to 2.62 µg/L. PSA in case 2 increased from 9.939 µg/L to 168.536 µg/L, and testosterone increased from 0.0 µg/L increased to 2.85 µg/L. PSA increased from 13.31 µg/L to 39.278 µg/L in case 3, testosterone increased from 0.0 µg/L to 2.54 µg/L. and PSA increased from 36.0 µg/L to 350.2 µg/L in the case 4, testosterone increased from 1.81 µg/L to 3.85 µg/L. Except for one patient who showed significant PSA remission, the PSA levels of the remaining three patients remained high overall. There were no adverse reactions reported in 4 patients. In the follow-up, case 1 continued to use PD-1 monoclonal antibody (median progression free survival time was 10 months). Two patients who had previously been resistant to enzalutamide received enzalutamide again after the whole cycle of treatment, and their PSA decreased again, which indicated that the patient was sensitive to enzalutamide again. BAT had a certain therapeutic effect on mCRPC patients, and the safety was controllable. Its tumor control effect still needed long-term follow-up verification in large-sample clinical trials. BAT has a certain therapeutic effect on mCRPC patient, especially the resensitivity of tumors to enzalutamide can be restored. Immune checkpoint inhibitors may have therapeutic potential in patients with prostate cancer treated with BAT and enzalutamide.

Taurine Reduces Liver Damage in Non-Alcoholic Fatty Liver Disease Model in Rats by Down-Regulating IL-9 and Tumor Growth Factor TGF-ß.

The study employed a rat model to examine the effects of taurine (Tau) on prevention and therapy of non-alcoholic fatty liver disease (NAFLD). In model rats maintained on a high-fat diet (HFD), the serum levels of ALT, AST, triglycerides, cholesterol, and LDL were higher than the corresponding levels in normal control and NP groups (p<0.05). In Tau-prevention and Tau-treatment groups, the serum levels of AST and triglycerides were lower than in HFD rats (p<0.05). In HFD rats, diffuse fatty degeneration and infiltration with inflammatory cells was observed in the liver; in the ileal mucosa, the villi were fractured or absent, the epithelium was exfoliated and infiltrated with inflammatory cells. The levels of TGF-ß, IL-9, and their mRNA in the liver and ileal mucosa of HFD rats were significantly higher than in normal control and NP groups (p<0.05). In Tau-prevention and Tau-treatment groups, these levels were significantly lower than in HFD rats (p<0.05). Thus, TGF-ß and IL-9 can be implicated in NAFLD genesis, while Tau can preventively or therapeutically diminish the damage to the liver and ileal mucosa in rats with this disease by down-regulating the expression of TGF-ß and IL-9.

Worldwide cancer statistics of adolescents and young adults in 2019: a systematic analysis of the Global Burden of Disease Study 2019.

BACKGROUND: The cancer burden in adolescents and young adults (AYAs) deserves more attention. However, global cancer statistics for AYAs are often presented as aggregates, concealing important heterogeneity. This study aimed to describe the worldwide profile of cancer incidence, mortality, and corresponding trends from 1990 to 2019 among 15-39-year olds by focusing on the patterns by age, sex, sociodemographic index (SDI), and regions. PATIENTS AND METHODS: Global, regional, and country data on the number of cancer cases and cancer-related deaths for 29 cancer types were collected from the 2019 Global Burden of Disease (GBD) Study. We also summarized the results using five levels of the SDI and 21 GBD regions. RESULTS: In 2019, an estimated 1 335 100 new cancer cases and 397 583 cancer-related deaths occurred among AYAs worldwide. While the incidence rate increased mildly, the death rate decreased significantly between 1990 and 2019, with an estimated annual percentage change of 0.38 (95% confidence interval 0.36-0.39) and -0.93 (95% confidence interval -0.95 to -0.92), respectively. The cancer burden was disproportionally greater among women than among men. The cancer profiles varied substantially across geographical regions, with the highest burden being in South Asia and East Asia. Besides, the cancer incidence in the high SDI regions was four times higher than that in the low SDI regions; however, the mortality burden in the high SDI region was lower than that in the low SDI region, which reflected the differences in cancer profiles across SDI regions and the inferior outcomes in the low SDI regions. CONCLUSION: This study updates the previous epidemiological data of the cancer burden of AYAs. The cancer burden in AYAs varied substantially according to age, sex, SDI, and geographical regions. These findings highlight that the specific cancer profile of AYA patients requires targeted cancer control measures to reduce the cancer burden in this age group.

[Surgical site infection after abdominal surgery in China: a multicenter cross-sectional study].

Objective: Surgical site infection (SSI) can markedly prolong postoperative hospital stay, aggravate the burden on patients and society, even endanger the life of patients. This study aims to investigate the national incidence of SSI following abdominal surgery and to analyze the related risk factors in order to provide reference for the control and prevention of SSI following abdominal surgery. Methods: A multicenter cross-sectional study was conducted. Clinical data of all the adult patients undergoing abdominal surgery in 68 hospitals across the country from June 1 to 30, 2020 were collected, including demographic characteristics, clinical parameters during the perioperative period, and the results of microbial culture of infected incisions. The primary outcome was the incidence of SSI within postoperative 30 days, and the secondary outcomes were ICU stay, postoperative hospital stay, cost of hospitalization and the mortality within postoperative 30-day. Multivariable logistic regression was used to analyze risk factors of SSI after abdominal surgery. Results: A total of 5560 patients undergoing abdominal surgery were included, and 163 cases (2.9%) developed SSI after surgery, including 98 cases (60.1%) with organ/space infections, 19 cases (11.7%) with deep incisional infections, and 46 cases (28.2%) with superficial incisional infections. The results from microbial culture showed that Escherichia coli was the main pathogen of SSI. Multivariate analysis revealed hypertension (OR=1.792, 95% CI: 1.194-2.687, P=0.005), small intestine as surgical site (OR=6.911, 95% CI: 1.846-25.878, P=0.004), surgical duration (OR=1.002, 95% CI: 1.001-1.003, P<0.001), and surgical incision grade (contaminated incision: OR=3.212, 95% CI: 1.495-6.903, P=0.003; Infection incision: OR=11.562, 95%CI: 3.777-35.391, P<0.001) were risk factors for SSI, while laparoscopic or robotic surgery (OR=0.564, 95%CI: 0.376-0.846, P=0.006) and increased preoperative albumin level (OR=0.920, 95%CI: 0.888-0.952, P<0.001) were protective factors for SSI. In addition, as compared to non-SSI patients, the SSI patients had significantly higher rate of ICU stay [26.4% (43/163) vs. 9.5% (514/5397), χ(2)=54.999, P<0.001] and mortality within postoperative 30-day [1.84% (3/163) vs.0.01% (5/5397), χ(2)=33.642, P<0.001], longer ICU stay (median: 0 vs. 0, U=518 414, P<0.001), postoperative hospital stay (median: 17 days vs. 7 days, U=656 386, P<0.001), and total duration of hospitalization (median: 25 days vs. 12 days, U=648 129, P<0.001), and higher hospitalization costs (median: 71 000 yuan vs. 39 000 yuan, U=557 966, P<0.001). Conclusions: The incidence of SSI after abdominal surgery is 2.9%. In order to reduce the incidence of postoperative SSI, hypoproteinemia should be corrected before surgery, laparoscopic or robotic surgery should be selected when feasible, and the operating time should be minimized. More attentions should be paid and nursing should be strengthened for those patients with hypertension, small bowel surgery and seriously contaminated incision during the perioperative period.

MiR-145 targeting BNIP3 reduces apoptosis of chondrocytes in osteoarthritis through Notch signaling pathway.

OBJECTIVE: The purpose of this study was to explore the effect of micro ribonucleic acid (miR)-145 on the apoptosis of chondrocytes in osteoarthritis (OA), and to research the association between its targeting on B-cell lymphoma-2 (Bcl-2)/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) and Notch signaling pathway and chondrocyte apoptosis. MATERIALS AND METHODS: The mouse model of OA was established via surgery, and chondrocytes were isolated and cultured in vitro. Then, the chondrocytes were transfected with miR-145 inhibitor, miR-145 mimics, miR-negative control (NC), BNIP3-siRNA and BNIP3-vector, respectively, with those normally cultured as the control. After that, the expression levels of miR-145 and BNIP3 in cells were detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), the apoptosis rate was detected via flow cytometry, and the apoptosis level was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the target gene sequences were predicted and compared using the software, and the BNIP3 Luciferase reporter vectors containing predicted target sites for miR-145 were constructed. Finally, the protein expressions of BNIP3, Notch1, and P21 were determined through Western blotting. RESULTS: The results of qRT-PCR showed that in OA chondrocytes, the expression of miR-145 was lower than that in normal chondrocytes (p<0.05), while the mRNA and protein expressions of BNIP3 were higher than those in normal chondrocytes (p<0.05). According to flow cytometry, the apoptosis rate was (4.4±0.6)% in normal cartilage tissues and (29.2±2.1)% in OA cartilage tissues. Overexpression of miR-145 significantly reduced chondrocyte apoptosis (p<0.05), while overexpression of BNIP3 markedly increased chondrocyte apoptosis (p<0.05). In addition, the Luciferase reporter system showed that miR-145 mimics evidently inhibited BNIP3 (p<0.05) and suppressed the Notch signaling pathway (p<0.05), while BNIP3 enhanced the expression of Notch signaling pathway (p<0.05). CONCLUSIONS: MiR-145 can reduce OA-induced chondrocyte apoptosis through targeted inhibition on BNIP3 and regulation on Notch signaling pathway.

MiRNA-203a-5p alleviates the malignant progression of Wilms' tumor via targeting JAG1.

OBJECTIVE: To uncover the potential influence of microRNA-203a-5p (miRNA-203a-5p) on the malignant progression of Wilms' tumor (WT). PATIENTS AND METHODS: MiRNA-203a-5p levels in 49 paired WT and paracancerous tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Prognostic value of miRNA-203a-5p in WT was assessed by the Kaplan-Meier method. Correlation between miRNA-203a-5p level and clinical data of WT patients was analyzed. In G401 and SK-NEP-1 cells, in vitro functions of miRNA-203a-5p in regulating metastatic abilities were explored. The interaction between miRNA-203a-5p and JAG1, and their regulatory role in the malignant progression of WT were evaluated by Dual-Luciferase reporter gene assay and rescue experiments. RESULTS: MiRNA-203a-5p was downregulated in WT tissues than that of paracancerous ones. WT patients expressing low level of miRNA-203a-5p had higher risk of lymphatic metastasis and worse prognosis. Overexpression of miRNA-203a-5p attenuated migratory and invasive abilities in G401 cells. On the contrary, knockdown of miRNA-203a-5p yielded the opposite trends in SK-NEP-1 cells. JAG1 was verified to be the direct gene binding miRNA-203a-5p, which was negatively regulated by miRNA-203a-5p in WT cells. Rescue experiments finally uncovered that miRNA-203a-5p alleviated the malignant progression of WT via negatively regulating JAG1. CONCLUSIONS: MiRNA-203a-5p is downregulated in WT and closely linked to lymphatic metastasis of WT patients. By negatively regulating JAG1, miRNA-203a-5p alleviates the malignant progression of WT.

Apelin-13/APJ system delays intervertebral disc degeneration by activating the PI3K/AKT signaling pathway.

OBJECTIVE: To study the effect of Apelin-13/APJ system on intervertebral disc degeneration and its mechanism. PATIENTS AND METHODS: This study detected the expression of APJ in human intervertebral disc tissue with varying degrees of degeneration. IL-1ß is used to stimulate the degeneration of nucleus pulposus cells. We used recombinant human Apelin-13 and Ala13 to activate and inhibit the APJ receptor, respectively. The inhibitor LY294002 was used to inhibit the PI3K/AKT signaling pathway. We studied the effects of Apelin-13/APJ system on nucleus pulposus cells and its mechanism by Western blot, RT-PCR, and so on. RESULTS: APJ is lowly expressed in the nucleus pulposus of patients with a high degree of degeneration. IL-1ß stimulates the nucleus pulposus cells and reduces the expression of APJ in nucleus pulposus cells. Recombinant human Apelin-13 reduces the degradation of nucleus pulposus extracellular matrix, promotes proliferation, and reduces the levels of apoptosis and inflammation. In addition, the Apelin-13/APJ system increases the expression of PI3K and AKT and activates the PI3K/AKT signaling pathway. CONCLUSIONS: Apelin-13/APJ system activates PI3K/AKT signaling pathway activity, reduces the degradation of nucleus pulposus extracellular matrix, promotes proliferation, and reduces the level of apoptosis and inflammation, thus delaying the degeneration of the intervertebral disc.

Denatonium as a bitter taste receptor agonist damages jejunal epithelial cells of yellow-feathered chickens via inducing apoptosis.

The sense of bitter taste is critical for chickens to acquire and select feeds. It is important to understand the roles and mechanisms of bitter taste transduction in chickens. Denatonium is extensively used as a bitter taste receptor agonist to activate bitter taste receptors in recent studies. The objective of this study was to investigate the physiological effects and the potential molecular mechanisms of dietary exposure to a strong bitter taste receptor agonist on the jejunal epithelial cells of yellow-feathered chickens. A total of 240 yellow-feathered chickens were divided into four treatments receiving a normal diet (Control), a low-dose denatonium treatment (Control + 5 mg/kg denatonium), a middle-dose denatonium treatment (Control + 20 mg/kg denatonium) and a high-dose denatonium treatment (Control + 100 mg/kg denatonium) for 56 days, respectively. The results showed that dietary denatonium reduced (P < 0.05) the growth performance of chickens. High-dose denatonium damaged the morphology of the jejunal epithelium and decreased (P < 0.05) the activities of Ca2+-ATPase, sucrase and maltase after 56 days of exposure. Meanwhile, high-dose denatonium increased (P < 0.05) mRNA expressions of bitter taste receptors, which resulted in enhanced apoptosis in jejunal epithelial cells after 56 days of exposure. Furthermore, middle-dose and high-dose denatonium exhibited increased (P < 0.05) mRNA level of claudin 2 and decreased (P < 0.05) mRNA level of occludin after 28 days of exposure. Only high-dose denatonium decreased (P < 0.05) mRNA level of occludin after 56 days of exposure. In conclusion, denatonium manifested deleterious effects on the jejunum of chickens in a dose-effect manner via damaging the morphology of the jejunal epithelium, and inducing apoptosis associated with bitter taste receptors. Our data suggest that bitter-tasting feed additives may have side effects on the growth and development of intestines in chickens.

LncRNA PVT1 aggravates the progression of glioma via downregulating UPF1.

OBJECTIVE: To uncover the influence of plasmacytoma variant translocation 1 (PVT1) on aggravating the progression of glioma via downregulating UPF1. PATIENTS AND METHODS: The relative levels of PVT1 and UPF1 in glioma tissues were determined. PVT1 level in glioma patients in stage I+II and stage III+IV, and either with metastasis or not was examined as well. The Kaplan-Meier curves were depicted for assessing the survival in glioma patients expressing a high and low level of PVT1. The regulatory effects of PVT1 and UPF1 on the proliferative and migratory abilities of U87 and LN229 cells were evaluated. The subcellular distributions of PVT1 and UPF1 were analyzed, and their interaction was investigated by performing RNA immunoprecipitation (RIP) assay. At last, the mRNA level of UPF1 was determined in U87 and LN229 cells overexpressing PVT1 treated with 50 µM α-amanitin. RESULTS: PVT1 was upregulated in glioma tissues relative to controls. Its level was higher in glioma patients with advanced stage or accompanied by metastasis. The glioma patients with a high level of PVT1 suffered a worse prognosis. The overexpression of PVT1 accelerated proliferative and migratory abilities of U87 and LN229 cells. UPF1 was conversely downregulated in glioma patients. Its level was negatively correlated to that of PVT1. The overexpression of UPF1 attenuated the proliferative and migratory abilities of U87 and LN229 cells. Both PVT1 and UPF1 were mainly enriched in the cytoplasm. The interaction between PVT1 and UPF1 was identified in the RIP assay. PVT1 prolonged the half-life of UPF1 and inhibited its synthesis. CONCLUSIONS: PVT1 accelerates the proliferative and migratory abilities of glioma via downregulating UPF1.

Genistein improves the reproductive performance and bone status of breeder hens during the late egg-laying period.

Genistein (GEN), a type of soy isoflavones, is similar to estrogen structurally and functionally. The effects of dietary gen on the reproductive performance and bone status of breeder hens were investigated. A total pf 720 laying broiler breeder (LBB) hens were randomly allocated into 3 groups with supplemental dietary GEN doses (0, 40, 400 mg/kg). Each treatment has 8 replicates of 30 birds. The results indicated that supplemental GEN significantly improved the egg production and eggshell strength of LBB hens. Dietary GEN was deposited into the egg yolk, which decreased malonaldehyde in the follicle and egg yolk. The levels of vitellogenin (VTG), progesterone, and follicle-stimulating hormone in the serum of GEN-treated groups were elevated compared with the control group. Furthermore, GEN treatment downregulated the mRNA expression of insulin-like growth factor binding protein in the fallopian tube, whereas 40 mg/kg GEN treatment upregulated estrogen receptor α expression. Both the mRNA expression of VTG-II in the liver and mRNA expression of amphiregulin in the fallopian tube were upregulated after 40 and 400 mg/kg GEN treatment. In the 400 mg/kg GEN-treated group, the levels of calcitonin and alkaline phosphatase in the serum were increased compared with the control group, which was consistent with the increased levels of calcium and phosphorus in the tibia. Supplemental GEN (400 mg/kg) improved the tibia strength of LBB hens, whereas 40 mg/kg GEN had better effects on laying performance. In summary, dietary GEN could improve the egg production and quality, as well as the bone status of LBB hens during the late egg-laying period.

Intratumoral Polymorphism of Peroxisome Proliferator-Activated Receptor Delta-87 T>C in Colorectal Cancer.

Peroxisome proliferator activated receptor delta (PPARD) is a nuclear receptor transcription factor whose single nucleotide polymorphism (SNP), especially PPARD-87 T>C (rs2016520), may play an important role in expression regulation of PPARD. But its expression patterns as well as contribution in colorectal cancer (CRC) are still controversial. In this study, whether the intratumoral heterogeneity of polymorphism of PPARD-87 T>C (rs2016520) existed and its influence in CRC were investigated. Tumor masses from primary CRC patients were collected during the operation of tumorectomy, specimens at the different sites of the same tumor mass were sampled and stored individually. The SNP of PPARD-87 T>C was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the expression of PPARD in vivo was observed by immunohistochemistry. The correlation of PPARD -87 T>C intratumoral polymorphism and the clinicopathological parameters of patients was analyzed statistically. Tumor samples were collected from 106 CRC patients (70 males and 36 females) with an average age of 61.04±13.67 years. A total number of 808 samples (7.60±1.60 per patient) were mainly harvested at peripheral superficial (n=376), central superficial (n=163), invasive front (n=112) and mesenteric cancer foci (n=42) of tumor tissues as well as cancerous adjacent mucosa (n=104). PCR-RFLP analysis showed that T/T (n=460, 56.9%) and T/C (n=334, 41.3%) were the main genotypes of -87 T>C among these samples. Furthermore, intratumoral genotype of -87 T>C was homogeneous in 90 patients and heterogeneous in other 16 patients. The intratumoral heterogeneity was related to patients' age (P=0.016), tumor location (P=0.011) and the grade of differentiation (P=0.022). For patients with intratumoral heterogeneity, immunochemistry showed the expressions of PPARD were not influenced by T/T or T/C genotypes. Intratumoral heterogeneity of PPARD-87 T>C wildly existed in CRC, and associated with patients' age, tumor location and differentiation. However, the immunochemistry assay revealed that there's no significant link between heterogeneity and expression of PPARD.

Targeting genes and signaling pathways of transcriptional suppressor ZHX2 in hepatocellular carcinoma: a Chromatin Immunoprecipitation-sequencing (ChIP-seq) investigation.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. The unclear molecular mechanisms underlying could provide important theoretical basis for the prevention and control of HCC. This study performed chromatin immunoprecipitation-sequencing (ChIP-seq) to analyze the binding sites between zinc fingers and homeoboxes 2 (ZHX2) and its genome-wide target genes, and bioinformatics was used to analyze their gene transcription regulation network. Immunohistochemistry was used to detect the ZHX2 expression in HCC, and its association with the clinicopathological characteristics of HCC. Results of RT-PCR and western blot showed the expression of ZHX2 in HepG2 cells was obviously lower compared with normal liver cells. ZHX2 could be amplified in ChIP products, then ChIP-seq reveals there were 232 genes binding in promoter regions. GO analysis of functions revealed these genes were mainly associated with biological processes (BP), cellular components (CC), and molecular functions (MF). In addition, PTEN was found enriched in certain biological functions in BP analysis. Then, four pathways of these genes based on Kyoto Encyclopedia of Genes and Genomes (KEGG) were found P<0.05. Last analysis of immunohistochemistry showed the rates of ZHX2 expression and PTEN expression in paracancerous tissues both were significantly higher than that in HCC tissues (P=0.042; P<0.001), with negative correlations with AFP values (r=-0.246, P=0.040; r=-0.263, P=0.028). Further, PTEN expression was positively correlated with the differentiation level in HCC tissues (r=0.267, P=0.025). Spearman correlation analysis revealed that the expression profiles of ZHX2 and PTEN were positively correlated in HCC tissues (r=0.258, P=0.031). This study is the first to use ChIP-seq technology to analyze the specific regulatory mechanisms of the transcription suppressor ZHX2 in the context of HCC at the genome level.

AID and TET2 co-operation modulates FANCA expression by active demethylation in diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is traced to a mature B malignance carrying abnormal activation-induced cytidine deaminase (AID) expression. AID activity initially focuses on deamination of cytidine to uracil to generate somatic hypermutation and class-switch recombination of the immunoglobulin (Ig), but recently it has been implicated in DNA demethylation of genes required for B cell development and proliferation in the germinal centre (GC). However, whether AID activity on mutation or demethylation of genes involves oncogenesis of DLBCL has not been well characterized. Our data demonstrate that the proto-oncogene Fanconi anaemia complementation group A (FANCA) is highly expressed in DLBCL patients and cell lines, respectively. AID recruits demethylation enzyme ten eleven translocation family member (TET2) to bind the FANCA promoter. As a result, FANCA is demethylated and its expression increases in DLBCL. On the basis of our findings, we have developed a new therapeutic strategy to significantly inhibit DLBCL cell growth by combination of the proteasome inhibitor bortezomib with AID and TET2 depletion. These findings support a novel mechanism that AID has a crucial role in active demethylation for oncogene activation in DLBCL.

[Value analysis of preoperative and intra-operative ultrasound in diagnosis and treatment of parathyroid adenoma].

Objective:To explore the value characteristics of preoperative and intra-operative ultrasound in the diagnosis and treatment of parathyroid adenoma,and to further clarify the value of ultrasound in the diagnosis and treatment of parathyroid adenoma.Method:A total of 62 cases of parathyroid adenoma confirmed by postoperative pathology from March 2016 to November 2017 were collected, and the pre-operative ultrasound parameters were analyzed;and 26 cases were detected by intra-operative ultrasound.Result:In 62 cases of parathyroid adenoma, 58 cases of parathyroid adenoma were diagnosed by ultrasound before operation,and the sensitivity was 93.54%. Among the 26 cases,the lesions of 24 cases were detected by intra-operative ultrasound,and the sensitivity was 92.31%.Conclusion:Preoperative ultrasonography has a high diagnostic value for the qualitative diagnosis and location diagnosis of parathyroid adenoma, and intra-operative ultrasound can help to detect lesions quickly and safely, which is of great significance to shorten the operation time and improve the safety of operation. It is an important development space of ultrasound in the diagnosis and treatment of parathyroid glands.

Expression of IL-17A, E, and F and their receptors in non-small-cell lung cancer.

Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Interaction of nascent or established lung tumour cells with various cytokines and infiltrating immune cells has been implicated in lung cancer pathogenesis. In this study, we systematically analysed immunoreactivity for IL-17A, IL-17E and IL-17F and their relevant receptors in the lung sections from non-small cell lung cancer (NSCLC) and normal control. Immunoreactivity for IL-17A, IL-17F, IL-17RA and IL- 17RC, but not IL-17RB was significantly elevated in NSCLC compared with controls, while IL-17E was reduced. The median numbers of infiltrating lymphocytes and neutrophils and global macrophage (CD68) immunoreactivity of phagocytes were also elevated in NSCLC compared with control tissue sections. Furthermore, correlation between the expression of IL-17A and its receptors IL-17RA and IL- 17RC varied according to NSCLC histopathological type. These data suggest that IL-17A, E, F and their receptors IL-17RA, RB, RC may be involved in the pathogenesis of NSCLC. Further understanding of the relationship between the IL-17/IL-17R axis and the tumour inflammatory microenvironment may reveal new therapeutic targets.

LncRNA NBAT-1 is down-regulated in lung cancer and influences cell proliferation, apoptosis and cell cycle.

OBJECTIVE: To explore the expression and role of lncRNA NBAT-1 in lung cancer. PATIENTS AND METHODS: LncRNA NBAT-1 expression in lung cancer tissues and adjacent areas was detected via reverse transcriptase-polymerase chain reaction (RT-PCR). RAC1 protein was analyzed via Western blotting assay. Cell counting kit-8 (CCK-8) and flow cytometry were used to evaluate cell proliferation and apoptosis as well as cell cycle. RESULTS: The expression level of lncRNA NBAT-1 in cancer specimen was remarkably lower than that in adjacent areas. Furthermore, the low expression of lncRNA NBAT-1 had a significant correlation with patient's tumor size, differentiation degree of tumor cells and lymph node metastasis. The overexpression of lncRNA NBAT-1 could inhibit the proliferation and cell cycle, promote the apoptosis of A549 cells, and down-regulate the expression level of RAC1. CONCLUSIONS: The low expression of lncRNA NBAT-1 is involved in the progression of lung cancer.

Glucose and lipid metabolism disorders in the chickens with dexamethasone-induced oxidative stress.

The purpose of this study was to investigate the effects of long-term treatment with dexamethasone (DEX) on the antioxidation and nutrition metabolism in broiler chickens. Broilers were placed on a high-nutrient diet for 41 days, and half were given orally DEX-supplemented water at 20 mg/L every other day from 19 to 41 days of age. DEX treatment downregulated superoxide dismutase activity as well as the mRNA expression of CuZn-superoxide dismutase and glutathione peroxidase with a decrease in GSH/GSSG ratio and an increase in malondialdehyde level in the liver of broilers. DEX treatment aggravated oxidative damage in the liver and, therefore, increased the sensitivity of broilers to ascites syndrome with higher mortality and reduced growth performance. Serum metabolomics analysis showed that DEX treatment significantly increased the levels of glucose, intermediates in protein metabolism (valine, proline, serine, threonine and urea) and lipid metabolism-related products (palmitic acid, stearic acid and cholesterol) while decreasing the levels of ß-hydroxy butyric acid, succinic acid and malic acid, demonstrating that DEX treatment inhibited the Krebs cycle and the oxidation of fatty acids, and promoted the de novo synthesis of fatty acids as well as protein decomposition in the liver of broilers. Additionally, detection of metabolism-related enzymes revealed that DEX treatment inhibited glycolysis and promoted glycogen decomposition. In summary, DEX treatment resulted in oxidative stress and glucose and lipid metabolism disorders in the broilers.