Molecular features, antiviral activity, and immunological expression assessment of interferon-related developmental regulator 1 (IFRD1) in red-spotted grouper (Epinephelus akaara).

Interferon-related developmental regulator 1 (IFRD1) is a viral responsive gene associated with interferon-gamma. Herein, we identified the IFRD1 gene (EaIFRD1) from red-spotted grouper (Epinephelus akaara), evaluated its transcriptional responses, and investigated its functional features using various biological assays. EaIFRD1 encodes a protein comprising 428 amino acids with a molecular mass of 48.22 kDa. It features a substantial domain belonging to the interferon-related developmental regulator superfamily. Spatial mRNA expression of EaIFRD1 demonstrated the highest expression levels in the brain and the lowest in the skin. Furthermore, EaIFRD1 mRNA expression in grouper tissues exhibited significant modulation in response to immune stimulants, including poly (I:C), LPS, and nervous necrosis virus (NNV) infection. We analyzed downstream gene regulation by examining type Ⅰ interferon pathway genes following EaIFRD1 overexpression. The results demonstrated a significant upregulation in cells overexpressing EaIFRD1 compared to the control after infection with viral hemorrhagic septicemia virus (VHSV). A subcellular localization assay confirmed the nuclear location of the EaIFRD1 protein, consistent with its role as a transcriptional coactivator. Cells overexpressing EaIFRD1 exhibited increased migratory activity, enhancing wound-healing capabilities compared to the control. Additionally, under H2O2 exposure, EaIFRD1 overexpression protected cells against oxidative stress. Overexpression of EaIFRD1 also reduced poly (I:C)-mediated NO production in RAW267.4 macrophage cells. In FHM cells, EaIFRD1 overexpression significantly reduced VHSV virion replication. Collectively, these findings suggest that EaIFRD1 plays a crucial role in the antiviral immune response and immunological regulation in E. akaara.

Development and validation of a risk assessment nomogram for venous thromboembolism associated with hospitalized postoperative Chinese breast cancer patients.

AIM: The purpose of this study was to develop and validate an individualized nomogram to predict venous thromboembolism (VTE) risk in hospitalized postoperative breast cancer patients. DESIGN: A single-central retrospective and non-interventional trial. METHODS: For model development, we used data from 4,755 breast cancer patients between 1 November 2016-30 June 2018 (3,310 patients in the development group and 1,445 in the validation group). Overall, 216 patients developed VTE (150 in development group and 66 in validation group). The model was validated by receiver operating characteristic curves and the calibration plot. The clinical utility of the model was determined through decision curve analysis. RESULTS: The individualized nomogram consisted of six clinical factors: age, body mass index, number of cardiovascular comorbidities, neoadjuvant chemotherapy, surgical treatment, hospital length of stay and two pre-operative biomarkers of Homocysteine and D-dimer. The model at the 3.9% optimal cut-off had the area under the curve of 0.854 (95% CI, 0.824-0.884) and 0.805 (95% CI, 0.740-0.870) in the development and validation groups. A p = 0.570 of the calibration test showed that the model was well-calibrated. The net benefit of the model was better between threshold probabilities of 5%-30% in decision curve analysis. CONCLUSION: The nomogram of VTE risk assessment, is applicable to hospitalized postoperative breast cancer patients. However, multi-central prospective studies are needed to improve and validate the model. Effectiveness and safety of thromboprophylaxis in high-risk patients are needed to demonstrate in interventional trials. IMPACT: This nomogram can be used in clinical to inform practice of physicians and nurses to predict the VTE probability and maybe direct personalized decision making for thromboprophylaxis in hospitalized postoperative breast cancer patients.

Leukemic IL-17RB signaling regulates leukemic survival and chemoresistance.

Secreted proteins provide crucial signals that have been implicated in the development of acute myeloid leukemia (AML) in the bone marrow microenvironment. Here we identify aberrant expressions of inflammatory IL-17B and its receptor (IL-17RB) in human and mouse mixed lineage leukemia-rearranged AML cells, which were further increased after exposure to chemotherapy. Interestingly, silencing of IL-17B or IL-17RB led to significant suppression of leukemic cell survival and disease progression in vivo. Moreover, the IL-17B-IL-17RB axis protected leukemic cells from chemotherapeutic agent-induced apoptotic effects. Mechanistic studies revealed that IL-17B promoted AML cell survival by enhancing ERK, NF-κB phosphorylation, and the expression of antiapoptotic protein B-cell lymphoma 2, which were reversed by small-molecule inhibitors. Thus, the inhibition of the IL-17B-IL-17RB axis may be a valid strategy to enhance sensitivity and therapeutic benefit of AML chemotherapy.-Guo, H.-Z., Niu, L.-T., Qiang, W.-T., Chen, J., Wang, J., Yang, H., Zhang, W., Zhu, J., Yu, S.-H. Leukemic IL-17RB signaling regulates leukemic survival and chemoresistance.

Music interventions for chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is the most common and severe side effects brought by chemotherapeutics. The role of music interventions in relieving CINV is uncertain. The aim of this systematic review was to test the effects of music interventions on three categories of CINV. METHODS: A systematic search was conducted in Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), WanFang, and Chinese Biomedical Database (CBM) in order to capture randomized controlled trials (RCTs) investigating the comparative efficacy of music interventions and others. Two investigators screened, sorted, and extracted the data, and appraised the risk of bias. All statistical analyses were performed using RevMan 5.3 software. RESULTS: The literature search yielded 608 studies of which only ten RCTs fulfilled the eligibility criteria with 632 patients retrieved. Although the duration, the frequency of interventions, and the type of selected music varied across studies, commonly used elements included music listening. Results showed that music interventions were associated with reducing the incidence of anticipatory CINV and lowering the severity of delayed vomiting (MD = - 0.65, 95% CI = - 1.08 to - 0.23). However, strongly controversial results existed in terms of reducing the incidence of acute and delayed CINV, the severity of acute CINV, the severity of delayed nausea, and improving patients' quality of life. CONCLUSIONS: Music interventions may effectively reduce the incidence of anticipatory CINV and relieve the severity of delayed vomiting in patients with chemotherapy based on limited data. However, the conclusion should be interpreted with caution and further research is required to design with large-scale and rigorous methods.

Development of death education training content for adult cancer patients: A mixed methods study.

AIMS AND OBJECTIVES: The aim of this mixed methods study was to develop science-based content for a systematic death education training system based on the needs of adult cancer patients. The study contained two parts: survey development and Delphi survey. First, a small sample test was conducted to check the reliability and validity of the questionnaire. Next, this questionnaire was applied to investigate adult cancer patients' needs for death education. Then, we invited experts in the fields of nursing management, clinical medicine, clinical nursing and psychological care to carry out two rounds of Delphi consultations to revise the training content. BACKGROUND: Death education is often combined with hospice care, which is based on a clear 6-month survival period. However, the survival of adult cancer patients has improved with improved cancer diagnoses and treatments, and death education should be initiated before the dying stage. At the same time, patients' needs for medical information become increasingly important in daily clinical practice. Therefore, a death education programme based on adult cancer patients' needs was developed to help these patients reflect on the meanings of life and death. DESIGN: A mixed methods study. METHODS: During the survey development period (from April 2017-September 2017), a small sample test (n = 150) was conducted to verify the reliability and validity of the questionnaire on death education needs of adult cancer patients. This questionnaire was developed based on a literature review and discussion among the study group. Next, 324 adults with cancer, recruited from a three-level cancer hospital in Tianjin, China, were surveyed to analyse their needs for death education, using the questionnaire that had been tested in the pretest period. Finally, a Delphi survey was conducted from October 2017-January 2018. A panel of experts (n = 23) recruited from major hospitals, nursing schools and universities in China in the fields of clinical nursing, nursing management, clinical medicine and psychological care took part in the study to revise the training contents based on the investigation results. RESULTS: The reliability and validity of results based on the small sample test revealed that the Cronbach's alpha coefficient and the half-degree of reliability of the questionnaire were 0.924 and 0.951, respectively. This demonstrated that the questionnaire had high reliability. The KMO was 0.756 and the Bartlett Test of Sphericity showed p < 0.001, indicating that the factor analysis was justified in the sample. Eight components with eigenvalues greater than one were retained by the factor analysis. The investigation of the patients' needs for death education showed that the overall score of patients' needs was 3.60 ± 0.709 points (needs were measured on a scale from 1-5, where 5 indicates high needs), and there were high demands for education regarding "cancer patient life reviews," "death-related ethical issues" and "to leave peacefully." Data from expert panel members were collected in two rounds over a 4-month period, and consensus was achieved in the second Delphi round. The final death education contents of adult cancer patients contained four sections: cancer, death, psychology and practice. These were divided into 54 teaching topics to be included in 14 courses. CONCLUSIONS: The adult cancer patient death education training content devised in this study is science-based, practical and can be used as a guide for clinical nurses to provide high-quality care to adult cancer patients. RELEVANCE TO CLINICAL PRACTICE: Nurses could become more involved in providing death education to adult cancer patients and their families. Further research is needed to explore the applicability of the training content and to develop the content according to changing times and patients' needs.

AngiotensinII induces HuR shuttling by post-transcriptional regulated CyclinD1 in human mesangial cells.

Abnormal proliferation of human mesangial cells was the earliest pathological character in chronic kidney disease and linked to the accumulation of extracellular matrix and glomerular sclerosis. Multifunctional Angiotensin (AngII) had been emerged as a key player in initiation and progression of fibrogenic processes in kidney. In mesangial cells, treatment with the proliferation stimulus AngII triggered the escalated cyclinD1 expression, where its association with HuR increased dramatically. In our study, it was demonstrated that both in vivo and in vitro HuR redistribution in dysregulated mesangial cell proliferation accompanied by an abundant cyclinD1 expression following the AngII treatment. ActinomycinD experiments revealed that AngII stabilized cyclinD1 mRNA in human mesangial cells via HuR. Furthermore, employing the RIP-Chip assay yielded cyclinD1 mRNA with a higher affinity to HuR in mesangial cells induced by AngII compared with the normal ones in vitro study. Analysis of a cyclinD1 mRNA directly implicated HuR in regulating cyclinD1 production: cyclinD1 translation increased in HuR-shuttling cells induced by AngII and declined in cells in which HuR levels were lowered by RNA interference. We proposed that the release of HuR-bound mRNAs via an AngII-cyclinD1-HuR regulatory axis was implicated in the evolution of proliferative kidney diseases, providing us a novel therapeutic strategy to treat glomerular disease.

Development and validation of a risk prediction model for breast cancer-related lymphedema in postoperative patients with breast cancer.

OBJECTIVE: Breast cancer-related lymphedema (BCRL) is a common post-operative complication in patients with breast cancer. Here, we sought to develop and validate a predictive model of BCRL in Chinese patients with breast cancer. METHODS: Clinical and demographic data on patients with breast cancer were collected between 2016 and 2021 at a Cancer Hospital in China. A nomogram for predicting the risk of lymphedema in postoperative patients with breast cancer was constructed and verified using R 3.5.2 software. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics, and the model was internally validated. RESULTS: A total of 1732 postoperative patients with breast cancer, comprising 1212 and 520 patients in the development and validation groups, respectively, were included. Of these 438 (25.39%) developed lymphedema. Significant predictors identified in the predictive model were time since breast cancer surgery, level of lymph node dissection, number of lymph nodes dissected, radiotherapy, and postoperative body mass index. At the 31.9% optimal cut-off the model had AUC values of 0.728 and 0.710 in the development and validation groups, respectively. Calibration plots showed a good match between predicted and observed rates. In decision curve analysis, the net benefit of the model was better between threshold probabilities of 10%-80%. CONCLUSION: The model has good discrimination and accuracy for lymphedema risk assessment, which can provide a reference for individualized clinical prediction of the risk of BCRL. Multicenter prospective trials are required to verify the predictive value of the model.

Can chronoradiotherapy offer benefits to cervical cancer patients? A scoping review.

The objective of this scoping review was to synthesize the available evidence and evaluate the effectiveness of chronoradiotherapy interventions in cervical cancer patients. This scoping review was performed by searching in the PubMed, Cochrane Library, Embase, Web of Science, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), China National Knowledge Infrastructure (CNKI), Wanfang, Wenpu, and Chinese Biomedical Literature (CBM) databases. Databases were searched for studies published in English or Chinese from inception to 21 May 2021, and reference lists of relevant reports were scanned. Two investigators independently screened eligible studies in accordance with predetermined eligibility criteria and extracted data. The included studies were summarized and analyzed. Five studies including a total of 422 patients with cervical cancer were included in the scoping review; four studies were Chinese, and one was Indian. Main themes identified included the efficiency of chronoradiotherapy and relevant toxic and side effects, including diarrhea toxicity, hematologic toxicity, myelosuppression, gastrointestinal mucositis, and skin reactions. Administration of radiotherapy at different times of the day resulted in similar efficacy. However, the toxic side effects of morning radiotherapy (MR) and evening radiotherapy (ER) differed, with radiotherapy in the evening leading to more severe hematologic toxicity and myelosuppression. There were conflicting conclusions about gastrointestinal reactions with chronoradiotherapy, and further studies are needed. Radiation responses may be associated with circadian genes, through the influence of cell cycles and apoptosis.

Israeli and Chinese partners of women with breast cancer: a cross-cultural view of marital issues.

OBJECTIVE: Cultural nuances may influence the interface between the cancer experience and marital issues, specifically for the partner. Most of the literature has focused on the woman's narrative or couple's adjustment to cancer in general. The purpose of this study was to describe and compare the marital relationship, sexuality, and marital adjustment of Israeli and Chinese husbands of women with breast cancer and the discussion of the health-care team concerning these issues. METHODS: A convenience sample of 50 Chinese and 50 Israeli men, ages of 28-79 years, completed components of the Psychological Adjustment to Illness Scale, the Locke Wallace Adjustment Scale, and a background questionnaire. RESULTS: The majority of husbands were in their first marriage. The average time since diagnosis was 16.7 months. No significant difference was found between the two groups on issues of marital relationship. Significant differences were found between Israeli and Chinese husbands on sexual interest, pleasure, and performance (p<0.05). Israeli husbands reported a significantly higher level of marital adjustment as opposed to the Chinese husbands (p = 0.006). Marital adjustment for both groups was significantly related only to perceived quality of the relationship (p<0.03). CONCLUSIONS: Significant cultural differences were found in sexuality variables with no differences discerned on marital relationship variables. Couple-based interventions for marital issues are a critical component of support for both partners. Culturally sensitive assessment and care of the spouse as well as the woman with breast cancer should be part of a holistic, comprehensive family care plan.

The effect of chronoradiotherapy on cervical cancer patients: A multicenter randomized controlled study.

Objectives: To investigate the short-term efficacy and radiotoxicity 3.543of chronoradiotherapy in patients with cervical cancer. We also examined the overall symptom score and quality of life (QOL) of patients who underwent morning radiotherapy and evening radiotherapy. Methods: We conducted a multicenter randomized controlled trial to compare the effects of morning radiotherapy (9:00-11:00 AM) with evening radiotherapy (7:00-9:00 PM) in cervical cancer patients receiving radiotherapy. From November 2021 to June 2022, 114 cervical cancer patients admitted to eight cancer center hospitals in Tianjin, Chongqing, Hubei, Shanxi, Shandong, Shaanxi, Hebei, and Cangzhou were randomly divided into the morning radiotherapy group (MG; N = 61) and the evening radiotherapy group (EG; N = 53). The short-term efficacy of radiotherapy on cervical cancer patients at different time points and the occurrence of radiotoxicity were explored after patients had undergone radiotherapy. Results: The total effective response (partial remission [PR] + complete remission [CR]) rate was similar across the two groups (93.5% vs. 96.3%, p > 0.05). However, the incidence of bone marrow suppression and intestinal reaction in the two groups were significantly different (p < 0.05). The patients in the MG had significantly higher Anderson symptom scores than patients in the EG (21.64 ± 7.916 vs. 18.53 ± 4.098, p < 0.05). In terms of physical activity, functional status, and overall QOL, the MG had significantly lower scores than the EG (p < 0.05). No other measures showed a significant difference between the groups. Conclusion: The radiotherapy effect of the MG was consistent with that of the EG. The incidence of radiation enteritis and radiation diarrhea in the MG was significantly higher than that in the EG; however, bone marrow suppression and blood toxicity in the EG were more serious than in the MG. Because of the small sample size of the study, we only examined the short-term efficacy of radiotherapy. Therefore, further clinical trials are needed to verify the efficacy and side effects of chronoradiotherapy. Clinical Trial Registration: http://www.chictr.org.cn/searchproj.aspx, Registration Number: ChiCTR2100047140.

Leukemic progenitor cells enable immunosuppression and post-chemotherapy relapse via IL-36-inflammatory monocyte axis.

Chemotherapy can effectively reduce the leukemic burden and restore immune cell production in most acute myeloid leukemia (AML) cases. Nevertheless, endogenous immunosurveillance usually fails to recover after chemotherapy, permitting relapse. The underlying mechanisms of this therapeutic failure have remained poorly understood. Here, we show that abnormal IL-36 production activated by NF-κB is an essential feature of mouse and human leukemic progenitor cells (LPs). Mechanistically, IL-36 directly activates inflammatory monocytes (IMs) in bone marrow, which then precludes clearance of leukemia mediated by CD8+ T cells and facilitates LP growth. While sparing IMs, common chemotherapeutic agents stimulate IL-36 production from residual LPs via caspase-1 activation, thereby enabling the persistence of this immunosuppressive IL-36­IM axis after chemotherapy. Furthermore, IM depletion by trabectedin, with chemotherapy and PD-1 blockade, can synergistically restrict AML progression and relapse. Collectively, these results suggest inhibition of the IL-36­IM axis as a potential strategy for improving AML treatment.

Association of polymorphisms of the acetyl-coA acetyltransferase 1 gene and the melatonin receptor 1B gene with the susceptibility to nonalcoholic fatty liver disease / 临床肝胆病杂志

ObjectiveTo investigate the association of the polymorphisms of the acetyl-CoA acetyltransferase 1 （ACAT1） gene and the melatonin receptor 1B （MTNR1B） gene with the susceptibility to nonalcoholic fatty liver disease （NAFLD）. MethodsA total of 164 healthy controls and 228 NAFLD patients were enrolled in this study. PCR and sequencing methods were used to determine the genotypes of the polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus， and fasting venous blood samples were collected for biochemical analysis. The t-test was used for comparison of normally distributed continuous data between groups， and the non-parametric Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. ResultsThere were no significant differences between the NAFLD group and the healthy control group in the genotype distribution of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus （all P>0.05）. The carriers of AA genotype at the rs1044925 locus of the ACAT1 gene had a significantly higher level of low-density lipoprotein than the carriers of C allele （Z=-2.08， P=0.04）， and the carriers of G allele at the rs10830963 locus of the MTNR1B gene had a significantly higher level of fasting blood glucose than the carriers of CC genotype （Z=-3.01， P<0.01）. ConclusionThe polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus were not associated with the susceptibility to NAFLD. The rs1044925 locus of the ACAT1 gene and the rs10830963 locus of the MTNR1B gene are associated with the levels of low-density lipoprotein and fasting blood glucose， respectively.

The health effects of Baduanjin exercise (a type of Qigong exercise) in breast cancer survivors: A randomized, controlled, single-blinded trial.

PURPOSE: This study aimed to evaluate the effectiveness of Baduanjin exercise, which is a traditional Chinese Qigong exercise, in breast cancer survivors to assess its efficacy for physical and psychological rehabilitation. METHODS: The study was a single-blinded randomized controlled trial. Eighty-six subjects were randomly assigned to the intervention (n = 46) or control (n = 40) groups. The intervention group received Baduanjin exercise 3 days/week at hospital and another 4 days/week at home for 6 months, whereas the control group were requested to maintain their original physical activity. Outcomes included body mass index (BMI), heart rate variability, lung capacity, arm circumference, shoulder range of motion, step test index, anxiety, depression, and quality of life (QOL). RESULTS: After 6 months of intervention, heart rate variability and shoulder range of motion were significantly improved in the Baduanjin group compared to the control group (P < 0.05). There were also significant improvements in depression, QOL, and four QOL dimension scores (physical well-being, social well-being, functional well-being, and breast cancer subscale) (P < 0.05). However, there were no differences in the BMI, lung capacity, arm circumference, step test index, anxiety, and the emotional well-being QOL dimension scores. CONCLUSION: Our findings indicate that Baduanjin is an effective intervention for improving physical and psychological health outcomes among breast cancer survivors, which is worth recommending and implementing by oncology nurses for breast cancer survivors during their long rehabilitation journeys.

Berberine Inhibits Atherosclerosis by Regulating Lipophagy Via Targeting Wnt5a/NPC1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the regulatory effect and molecular mechanism of berberine （BBR） on lipophagy in the prevention and treatment of atherosclerotic （AS） lesions in mice. MethodFifty apolipoprotein E-knockout （ApoE-/-） mice were randomly divided into an AS model group， an atorvastatin group （5 mg·kg-1）， and low-， medium-， and high-dose BBR groups （2.5， 5， 10 mg·kg-1）. Ten C57BL/6J mice were assigned to the control group. After 12 weeks， hematoxylin-eosin （HE） and oil red O staining were performed to assess the histopathological changes of AS plaques in the aorta. Biochemical analysis was used to measure serum lipid levels， and enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory cytokines interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）， oxidative stress marker reactive oxygen species （ROS）， and serum lipophagy marker Beclin1 and microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ）. The xanthine oxidase method was used to measure serum superoxide dismutase （SOD） activity. Immunohistochemistry （IHC） was used to detect the distribution of wingless-type MMTV integration site family member 5a （Wnt5a） and Nieman Pick type C1 （NPC1） in the aorta， and Western blot was used to determine the protein expression of Wnt5a and NPC1 in the aorta. ResultCompared with the control group， the AS model group showed significant AS plaque formation， significantly elevated levels of serum total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， IL-6， TNF-α， and ROS， aortic Wnt5a distribution and protein expression （P<0.01）， and significantly reduced levels of serum high-density lipoprotein cholesterol （HDL-C）， SOD， Beclin1， LC3Ⅱ， and aortic NPC1 distribution and protein expression （P<0.01）. Compared with the AS model group， the atorvastatin group， and high- and medium-dose BBR groups showed a significant reduction in AS plaque area （P<0.05， P<0.01）， significantly decreased levels of serum TC， TG， LDL-C， IL-6， TNF-α， ROS， and aortic Wnt5a distribution and protein expression （P<0.05， P<0.01）， and significantly increased levels of serum HDL-C， SOD， Beclin1， LC3Ⅱ， and aortic NPC1 distribution and protein expression （P<0.05， P<0.01）. There was no statistically significant difference in the above indicators between the atorvastatin group and the medium-dose BBR group. ConclusionBBR can competitively bind to Wnt5a to activate NPC1 expression， upregulate lipophagy levels， reduce blood lipids， and inhibit the release of inflammatory mediators and oxidative stress damage， thereby exerting a preventive and therapeutic effect on AS.

Anemoside B4 regulates fatty acid metabolism reprogramming in mice with colitis-associated cancer / 中国中药杂志

The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and β-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.

Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKalpha.

Insufficient intracellular fat oxidation is an important contributor to aging-related insulin resistance, while the precise mechanism underlying is unclear. AMP-activated protein kinase (AMPK) is an important regulator of intracellular fat oxidation and was evidenced to play a key role in high-glucose and high-fat induced glucose intolerance. In the present study, we investigated whether altered AMPK expression or activity was also involved in aging-related insulin resistance. Insulin sensitivity of rats' skeletal muscles was evaluated using in-vitro glucose uptake assay. Activity of alpha subunit of AMPK (AMPKalpha) was evaluated by measuring the phosphorylation of both AMPKalpha (P-AMPKalpha) and acetyl-CoA carboxylase (P-ACC), while expression of AMPKalpha was assessed by determining the mRNA levels of AMPKalpha1 and AMPKalpha2, and protein contents of AMPKalpha. Compared with 4-month old rats, 24-month old rats exhibited obviously impaired insulin sensitivity. At the same time, AMPKalpha activity significantly decreased, while AMPKalpha expression did not alter during aging. Glucose transporter 4 expression also decreased in old rats. Compared with 24-month old rats, administration of the specific activator of AMPK, 5-aminoimidazole-4-carboxamide riboside (AICAR), significantly elevated AMPKalpha activity and GluT4 expression. Also, aging-related insulin resistance was significantly ameliorated by AICAR treatment. In conclusion, aging-related insulin resistance is associated with impaired AMPKalpha activity and could be ameliorated by AICAR, thus indicating a possible role of AMPK in aging-induced insulin resistance.

A galectin related protein from Oplegnathus fasciatus: Genomic, molecular, transcriptional features and biological responses against microbial pathogens.

Galectins, a family of ß-galactoside-binding lectins, are pattern recognition receptors that recognize pathogen-associated molecular patterns and are subsequently involved in the opsonization, phagocytosis, complement activation, and killing of microbes. Here, we report a novel galectin related protein (GRP) identified from rock bream (Oplegnathus fasciatus), designated OfGal like B. The cDNA of OfGal like B is 517 bp with an open reading frame (ORF) of 438 bp, encoding 145 amino acids, with a single carbohydrate recognition domain (CRD). However, only two of the seven critical residues responsible for carbohydrate recognition were identified in the CRD. There was no signal peptide identified in the OfGal like B protein. The genomic structure of OfGal like B, determined using a bacterial artificial chromosome (BAC) genomic library, consists of four exons and three introns. Homology assessment, multiple sequence alignment, and phylogenetic analysis indicated that OfGal like B is an evolutionarily conserved lectin that is closely related to the proto-type galectins. OfGal like B mRNA was constitutively expressed in a wide range of tissues in healthy rock breams. When challenged with bacterial or viral stimulants, OfGal like B was up-regulated in the gills and spleen of rock breams, indicating that it likely plays an important role during bacterial and viral infections. Furthermore, recombinant OfGal like B (rOfGal like B) lacked carbohydrate-binding activity but was able to recognize and agglutinate bacteria, including Streptococcus iniae, Listeria monocytogenes, Vibrio tapetis, Escherichia coli, and Edwardsiella tarda, and a ciliate parasite, Miamiensis avidus. These results collectively suggest that OfGal like B is involved in pathogen recognition and plays a significant role(s) in the innate defense mechanism of rock bream.

[Clinical significance of expression of PSA, hK2, PSMA in the peripheral blood of patients with prostate cancer].

OBJECTIVE: To find sensitive and specific micro-metastic markers for prostate cancer. METHODS: Using nested reverse transcription-PCR, we examined the expression of PSA, hK2 and PSMA mRNA in peripheral blood mononuclear cells of 51 patients with prostate cancer, 33 patients with benign prostate hyperplasia (BPH) and 32 normal young people. RESULTS: The expression rates of PSA, hK2 and PSMA mRNA were 52.9%, 43.1% and 64.7%, respectively in prostate cancer group, and 6.2%, 7.7% and 4.6%, respectively in control group (BPH patients and normal young people) with statistical significance (P < 0.01). Although the expression rate of PSA and hK2 mRNA increased with cancer progression, there was no statistical significance among patients in different stages. The expression rate of PSMA mRNA was higher than that of PSA and hK2 mRNA in each clinical stage. CONCLUSION: PSMA mRNA expression detected by nested RT-PCR is of greater value for the diagnosis, therapy choice and prognostic evaluation of prostate cancer patients.

[Myocardial protective effect of ulinastatin against ischemia/reperfusion injury during open heart surgery with cardiopulmonary bypass].

OBJECTIVE: To investigate the protective effect of ulinastatin on myocardium against ischemia-reperfusion injury in open heart surgery with cardiopulmonary bypass (CPB). METHODS: Twenty ASA I-II patients undergoing atrioseptopexy or surgical repair of ventricular septal defect under CPB were randomly divided into two groups of 10 patients. The patients in the ulinastatin group (U), 5 males and 5 females, aged 6.7 +/- 2.6, received ulinastatin 12,000 unit/kg, half of the dose being given intravenously 10 min before aorta cannulation and another half being added into the priming fluid. The patients in the control group (C), 6 males and 4 females, aged 5.9 +/- 2.7, received the same volume of normal saline instead of ulinastatin. Arterial blood samples were taken before CPB (T1), at release of the aortic cross-clamp (T2), 30 min after aortic release (T3), 4 h and 24 h after discontinuation of CPB (T4, T5) for determination of plasma levels of cardiac troponin I (cTnI), creatine phosphokinase (CK) and creatine phosphokinase isoenzyme (CK-MB). RESULTS: The CPB time, aortic cross-clamping time and duration of operation were comparable between these 2 groups. The plasma cTnI level and CK and CK-MB activities were all within normal range before CPB in both groups. In group C the plasma level of cTnI started to increase at T2, peaked at T4 and started to decrease at T5. In group U the plasma levels of cTnI at T3 and T4 were significantly higher than the baseline value (both P<0.01) and returned to the baseline value at T5. The plasma cTnI levels at T(3-5) were significantly lower in group U than in group C (all P<0.01). The plasma CK and CK-MB activities increased significantly at T(2-5) in both groups (all P<0.01). There was no significant difference in plasma CK and CK-MB activity at T(2-4) between the two groups, but at T5 their activities were significantly lower in group U than in group C (P<0.05). The rate of spontaneous recovery of heart beat without defibrillation was higher in group U (8/10) than in group C (4/10) (P<0.05). The drainage volume during the 24 hours after operation was greater in group C than in group U (P<0.05). CONCLUSION: Ulinastatin effectively protects myocardium from ischemia-reperfusion injury during open heart surgery with CPB.

Prediction of the consistency of large pituitary adenoma based on CT density combined with texture parameter modeling / 中国医学影像技术

Objective: To explore the value of CT density combined with texture parameters based on CT plain image in predicting the consistency of large pituitary adenoma. Methods: Totally 50 patients with large pituitary adenoma confirmed by operation and pathology were enrolled and divided into soft group (n=30) and hard group (n=20) according to intraoperative pituitary consistency. The largest slice of the tumor on the CT image was selected, then ROI was manually outlined, CT value of the lesion was measured, and the texture feature parameters were extracted. CT values and texture features were compared between the two groups. Multivariate Logistic regression analysis was used to analyze the variables, and the model for predicting the pituitary adenoma consistency was established. ROC curve was drawn to evaluate its predictive value. Results: There was statistically significant difference in CT value between soft group and the hard group (P=0.031), and AUC in predicting tumor consistency was 0.662. A total of 77 texture parameters were extracted based on plain CT images, and 4 texture parameters were found with statistically significant differences between the two groups, including the Quantile 90, inertia, variance and contrast, with AUC of 0.662, 0.663, 0.672 and 0.663, respectively. AUC of texture feature model established with multivariate Logistic regression analysis in predicting the pituitary adenoma consistency was 0.690, of CT value combined with the texture parameter model was 0.782. Conclusion: The model established with CT value combined with texture parameters has high value in predicting the pituitary adenoma consistency, which is helpful to clinical selection of surgical plans.