Single-cell RNA sequencing reveals recruitment of the M2-like CCL8high macrophages in Lewis lung carcinoma-bearing mice following hypofractionated radiotherapy.

BACKGROUND: Tumor-associated macrophages (TAMs) play a pivotal role in reshaping the tumor microenvironment following radiotherapy. The mechanisms underlying this reprogramming process remain to be elucidated. METHODS: Subcutaneous Lewis lung carcinoma (LLC) murine model was treated with hypofrationated radiotherapy (8 Gy × 3F). Single-cell RNA sequencing was utilized to identify subclusters and functions of TAMs. Multiplex assay and enzyme-linked immunosorbent assay (ELISA) were employed to measure serum chemokine levels. Bindarit was used to inhibit CCL8, CCL7, and CCL2. The infiltration of TAMs after combination treatment with hypofractionated radiotherapy and Bindarit was quantified with flow cytometry, while the influx of CD206 and CCL8 was assessed by immunostaining. RESULTS: Transcriptome analysis identified a distinct subset of M2-like macrophages characterized by elevated Ccl8 expression level following hypofractionated radiotherapy in LLC-bearing mice. Remarkbly, hypofractionated radiotherapy not only promoted CCL8high macrophages infiltration but also reprogrammed them by upregulating immunosuppressive genes, thereby fostering an immunosuppressive tumor microenvironment. Additioinally, hypofractionated radiotherapy enhanced the CCL signaling pathway, augmenting the pro-tumorigenic functions of CCL8high macrophages and boosting TAMs recruitment. The adjunctive treatment combining hypofractionated radiotherapy with Bindarit effectively reduced M2 macrophages infiltration and prolonged the duration of local tumor control. CONCLUSIONS: Hypofractionated radiotherapy enhances the infiltration of CCL8high macrophages and amplifies their roles in macrophage recruitment through the CCL signaling pathway, leading to an immunosuppressive tumor microenvironment. These findings highlight the potential of targeting TAMs and introduces a novel combination to improve the efficacy of hypofractionated radiotherapy.

Fisetin suppresses chondrocyte senescence and attenuates osteoarthritis progression by targeting sirtuin 6.

Osteoarthritis (OA) is the most common type of arthritis and is an age-related joint disease that is particularly prevalent in subjects over 65 years old. The chronic rise of senescent cells has a close correlation with age-related diseases such as OA, and the senescence-associated secretory phenotype (SASP) is implicated in OA cartilage degeneration pathogenesis. Sirtuin 6 (SIRT6) is likely to be a key senescence-related regulator. Fisetin (FST) is a natural flavonol of the flavonoid family that is recommended as a senolytic drug to extend health and lifespan. However, the potential chondroprotective effects of FST on OA rats are largely unclarified. The aim of this study is to investigate the ameliorative effects of FST on OA joint cartilage and the relationship with SIRT6 and the detailed mechanisms from anti-inflammatory and anti-senescent perspectives. Rats were subjected to destabilization of the medial meniscus (DMM) surgery as a means of inducing the experimental OA model in vivo. Chondrocytes treated with IL-1ß were utilized for mimicking the OA cell model in vitro. Intra-articular injection of FST, OSS_128,167 (OSS, SIRT6 inhibitor), and MDL800 (MDL, SIRT6 agonist) in vivo or administering them in IL-1ß-induced rat chondrocytes in vitro were performed in order to determine the effects FST has on OA and the link with SIRT6. This study found SIRT6 level to be negatively correlated with OA severity. SIRT6 downregulation was validated in the joint cartilages of DMM rats and IL-1ß-treated chondrocytes. It was also notably demonstrated that FST can activate SIRT6. Both the administration of FST and activation of SIRT6 using MDL were found to rescue cartilage erosion, decrease extracellular matrix (ECM) degradation, prevent cartilage from apoptosis, and improve detrimental senescence-related phenotype. The alleviative effects of FST against inflammation, ECM degradation, apoptosis, and senescence in IL-1ß-stimulated chondrocytes were also confirmed. SIRT6 loss occurs in articular cartilage in OA pathogenesis, which is linked to aging. FST attenuates injury-induced aging-related phenotype changes in chondrocytes through the targeting of SIRT6.

Dietary resveratrol supplementation on growth performance, immune function and intestinal barrier function in broilers challenged with lipopolysaccharide.

This study discusses the effects of resveratrol (RES) on the productive performance, immune function and intestinal barrier function of broiler chickens challenged with lipopolysaccharide (LPS). Two hundred and forty 1-day-old male Arbor Acres broilers were randomly divided into 4 groups of 6 replicates each, with 10 broilers per replicate. This experiment used a 2 × 2 factorial design with dietary factors (basal diets or basal diets supplemented with 400 mg/kg RES were administered from d 1 to 21) and stress factors (intraperitoneal injection of 0.5 mg/kg BW of saline or LPS at 16, 18 and 20 d of age). The results showed that LPS challenge had a significant adverse effect on average daily gain (ADG) in broilers at 16 to 21 d of age (P < 0.05), whereas the addition of RES to the diet inhibited the LPS-induced decrease in ADG (P < 0.05). RES also alleviated LPS-induced immune function damage in broilers, which was manifested by the decrease of spleen index (P < 0.05) and the recovery of serum immunoglobulin M and ileal secretory immunoglobulin A content (P < 0.05). The LPS challenge also disrupts intestinal barrier function and inflammation, and RES mitigates these adverse effects in different ways. RES attenuated LPS-induced reduction of villus height in the jejunum and ileum of broilers (P < 0.05). LPS also caused an abnormal increase in plasma D-lactic acid levels in broilers (P < 0.05), which was effectively mitigated by RES (P < 0.05). LPS challenge resulted in a significant decrease in mRNA expression of occludin in the intestinal mucosa (P < 0.05), which was mitigated by the addition of RES (P < 0.05). RES significantly decreased the mRNA expression of toll-like receptor 4, nuclear factor kappa-B and tumor necrosis factor alpha in the ileum tissue stimulated by LPS (P < 0.05). Taken together, this study shows that RES exerts its beneficial effect on broilers challenged with LPS by alleviating immune function damage, relieving intestinal inflammation and barrier damage, and thus improving growth performance.

Preoperative frailty assessment could be a predictive factor for the prognosis of elderly patients undergoing coronary artery bypass grafting: a retrospective case-control study.

BACKGROUND: Frailty has been considered to be associated with major mortality and increased length of stay after cardiac surgery. This study aimed to explore the predictive potential of frailty assessment in the prognosis of elderly patients undergoing bypass surgery. METHODS: This study assessed the preoperative frailty according to the Fried's frailty phenotype, and included 150 frail and 150 non-frail elderly patients (≥ 65 y) who underwent bypass surgery. The present study evaluated the prognosis of elderly patients based on sequential organ failure assessment (SOFA) score, and collected clinical indicators to construct logistic regression models with the prognosis as the dependent variable, to explore the potential predictive ability of preoperative frailty. Moreover, this study focused on the complications and analyzed the relationship between preoperative frailty and postoperative complications. RESULTS: In the present study, 244 patients were divided into the favorable prognosis group and 56 patients were divided into the unfavorable prognosis group. Logistic regression analysis showed that increased myoglobin and high cardiac function classification were independent risk factors for unfavorable prognosis in elderly patients undergoing bypass surgery. The discrimination of the clinical prediction model was determined by the receiver operating characteristic (ROC) curve, and the area under curve (AUC) was 0.928. After adding preoperative frailty assessment, the AUC was improved to 0.939. This study found a significant correlation between preoperative frailty and postoperative complications, mainly in the circulatory system. CONCLUSION: Preoperative frailty assessment could be a predictive factor for the prognosis of elderly patients undergoing coronary artery bypass grafting. According to our study, frailty assessment and appropriate intervention before bypass surgery may be beneficial to the enhanced recovery after cardiac surgery. TRIAL REGISTRATION: The clinical study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (2021-SR-393). All patients signed an informed consent form.

Association Between the Early Serum Lipid Metabolism Profile and Delayed Neurocognitive Recovery After Cardiopulmonary Bypass in Cardiac Surgical Patients: a Pilot Study.

Cardiac surgery with extracorporeal circulation is considered to be one of the surgical types with the highest incidence of delayed neurocognitive recovery (DNR), but the mechanism is unclear. Metabolomics technology can be used to understand the early postoperative metabolic profile and find the relationship between serum metabolites and disease. We performed untargeted analyses of postoperative serum metabolites in all surgical groups, as well as serum metabolites in healthy nonsurgical adults, by using liquid chromatography‒mass spectrometry (LC‒MS). DNR after cardiopulmonary bypass surgery occurred in 35% of surgical patients. Sixty-nine metabolites were found to be associated with DNR. Lipids and lipid-like molecules occupy a total of 55 positions. Lipid metabolism occupies an important position in the serum metabolic profile of DNR patients in the early postoperative period. Phosphatidylinositol (PI), sphingomyelin (SM), and phosphatidylglycerol (PG) appear at the highest frequency. Correlation analysis and receiver operator characteristic curve analysis confirmed PI and SM as potential biomarkers for an increased risk of DNR.

Radiation-induced eosinophil increase ratio predicts patient outcomes in non-small celllung cancer.

Background and purpose: Radiotherapy (RT) is a double-edged sword in regulating immune responses. This study aimed to investigate the impact of thoracic RT on circulating eosinophils and its association with patient outcomes in non-small cell lung cancer (NSCLC). Materials and methods: This retrospective study included 240 patients with advanced NSCLC treated with definitive thoracic RT from January 2012 to January 2020. Statistics included Kaplan-Meier analysis of overall survival (OS) and progression-free survival (PFS), multivariate Cox analyses to identify significant variables, and Spearman's correlation to qualify the relationship between dose-volume histogram (DVH) parameters and EIR. Results: Absolute eosinophil counts (AECs) showed an increasing trend during RT and an obvious peak in the 1st month after RT. Thresholds of eosinophil increase ratio (EIR) at the 1st month after RT for both OS and PFS were 1.43. Patients with high EIR above 1.43 experienced particularly favorable clinical outcomes (five-year OS: 21% versus 10%, P<0.0001; five-year PFS: 10% versus 8%, P=0.014), but may not derive PFS benefit from the addition of chemotherapy to RT. The higher a patient's EIR, the larger the potential benefit in the absence of chemotherapy. DVH parameters including heart mean dose and heart V10 were negatively associated with EIR. None of these DVH parameters was correlated with the clinical outcomes. Conclusion: EIR may serve as a potential biomarker to predict OS and PFS in NSCLC patients treated with RT. These findings require prospective studies to evaluate the role of such prognostic marker to identify patients at risk to tailor interventions.

The Crosstalk Between Immune Infiltration, Circulating Tumor Cells, and Metastasis in Pancreatic Cancer: Identification of HMGB3 From a Multiple Omics Analysis.

Metastasis is the major cause of death in patients with pancreatic ductal adenocarcinoma (PDAC), and circulating tumor cells (CTCs) play an important role in the development of metastasis. However, few studies have uncovered the metastasis mechanism of PDAC based on CTCs. In this study, the existing bulk RNA-sequencing (bulk RNA-seq) and single-cell sequencing (scRNA-seq) data for CTCs in pancreatic cancer were obtained from the Gene Expression Omnibus (GEO) database. Analysis of tumor-infiltrating immune cells (TIICs) by CIBERSORT showed that the CTCs enriched from the peripheral blood of metastatic PDAC were found to contain a high proportion of T cell regulators (Tregs) and macrophages, while the proportion of dendritic cells (DCs) was lower than that enriched from localized PDAC. Through weighted gene co-expression network analysis (WGCNA) and the result of scRNA-seq, we identified the hub module (265 genes) and 87 marker genes, respectively, which were highly associated with metastasis. The results of functional enrichment analysis indicated that the two gene sets mentioned above are mainly involved in cell adhesion and cytoskeleton and epithelial-mesenchymal transition (EMT). Finally, we found that HMGB3 was the hub gene according to the Venn diagram. The expression of HMGB3 in PDAC was significantly higher than that in normal tissues (protein and mRNA levels). HMGB3 expression was significantly positively correlated with both EMT-related molecules and CTC cluster-related markers. Furthermore, it was also found that HMGB3 mutations were favorably related to tumor-associated immune cells through the TIMER2.0 online tool. We further demonstrated that PDAC patients with higher HMGB3 expression had significantly worse overall survival (OS) in multiple datasets. In summary, our study suggests that HMGB3 is a hub gene associated with EMT in CTCs, the formation of CTC clusters, and infiltration patterns of immune cells favorable for tumor progression and metastasis to distant organs.

Faecal microbiome and metabolic signatures in rectal neuroendocrine tumors.

Background: The prevalence of rectal neuroendocrine tumors (RNET) has increased substantially over the past decades. Little is known on mechanistic alteration in the pathogenesis of such disease. We postulate that perturbations of human gut microbiome-metabolome interface influentially affect the development of RNET. The study aims to characterize the composition and function of faecal microbiome and metabolites in RNET individuals. Methods: We performed deep shotgun metagenomic sequencing and untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomic profiling of faecal samples from the discovery cohort (18 RNET patients, 40 controls), and validated the microbiome and metabolite-based classifiers in an independent cohort (15 RNET participants, 19 controls). Results: We uncovered a dysbiotic gut ecological microenvironment in RNET patients, characterized by aberrant depletion and attenuated connection of microbial species, and abnormally aggregated lipids and lipid-like molecules. Functional characterization based on our in-house and Human Project Unified Metabolic Analysis Network 2 (HUMAnN2) pipelines further indicated a nutrient deficient gut microenvironment in RNET individuals, evidenced by diminished activities such as energy metabolism, vitamin biosynthesis and transportation. By integrating these data, we revealed 291 robust associations between representative differentially abundant taxonomic species and metabolites, indicating a tight interaction of gut microbiome with metabolites in RNET pathogenesis. Finally, we identified a cluster of gut microbiome and metabolite-based signatures, and replicated them in an independent cohort, showing accurate prediction of such neoplasm from healthy people. Conclusions: Our current study is the first to comprehensively characterize the perturbed interface of gut microbiome and metabolites in RNET patients, which may provide promising targets for microbiome-based diagnostics and therapies for this disorder.

Radiation-induced PD-L1 expression in tumor and its microenvironment facilitates cancer-immune escape: a narrative review.

Background and Objective: Radiotherapy (RT) is one of the fundamental anti-cancer regimens by means of inducing in situ tumor vaccination and driving a systemic anti-tumor immune response. It can affect the tumor microenvironment (TME) components consisting of blood vessels, immunocytes, fibroblasts, and extracellular matrix (ECM), and might subsequently suppress anti-tumor immunity through expression of molecules such as programmed death ligand-1 (PD-L1). Immune checkpoint inhibitors (ICIs), especially anti-programmed cell death 1 (PD-1)/PD-L1 therapies, have been regarded as effective in the reinvigoration of the immune system and another major cancer treatment. Experimentally, combination of RT and ICIs therapy shows a greater synergistic effect than either therapy alone. Methods: We performed a narrative review of the literature in the PubMed database. The research string comprised various combinations of "radiotherapy", "programmed death-ligand 1", "microenvironment", "exosome", "myeloid cell", "tumor cell", "tumor immunity". The database was searched independently by two authors. A third reviewer mediated any discordance of the results of the two screeners. Key Content and Findings: RT upregulates PD-L1 expression in tumor cells, tumor-derived exosomes (TEXs), myeloid-derived suppressor cells (MDSCs), and macrophages. The signaling pathways correlated to PD-L1 expression in tumor cells include the DNA damage signaling pathway, epidermal growth factor receptor (EGFR) pathway, interferon gamma (IFN-γ) pathway, cGAS-STING pathway, and JAK/STATs pathway. Conclusions: PD-L1 upregulation post-RT is found not only in tumor cells but also in the TME and is one of the mechanisms of tumor evasion. Therefore, further studies are necessary to fully comprehend this biological process. Meanwhile, combination of therapies has been shown to be effective, and novel approaches are to be developed as adjuvant to RT and ICIs therapy.

Long-term survival after partial hepatectomy for sub-stage patients with intermediate stage hepatocellular carcinoma.

BACKGROUND: The current study aimed to examine the long-term survival after partial hepatectomy for patients with BCLC intermediate stage hepatocellular carcinoma (HCC) stratified by the Bolondi's sub-staging model. MATERIALS AND METHODS: This cohort consisted of 360 patients with BCLC intermediate stage HCC who underwent partial hepatectomy between January 2008 and February 2010. Patients were stratified into 3 subgroups (B1-B3) based on the Bolondi's sub-staging model. The last follow-up was conducted at February 2014. RESULTS: Of these patients, 166, 171 and 23 patients had B1, B2, and B3 sub-stage HCC, respectively. The postoperative 5-year Overall survival (OS) rate for patients with these three sub-stages was 49.5%, 33.7% and 12.9%, respectively (P < 0.001). Compared with the reported survival outcomes from previous studies which used transarterial chemoembolization (TACE) as first-line treatment, hepatectomy had a better median survival than TACE in B1 and B2 patients. On multivariable analysis, presence of esophageal and gastric varices, higher NDR score, presence of microvascular invasion, differentiation grade III-IV, and patterns of AFP decreases after surgery were the independent risk factors of OS in the sub-stages B1 and B2 patients. A nomogram which integrated all these independent risk factors was developed, with a C-index of 0.71 for OS prediction. The calibration curve showed an optimal agreement between prediction by the nomogram and actual observation. CONCLUSIONS: The patients with intermediate stage HCC clarified as sub-stages B1 and B2 according to Bolondi's model had an optimal long-term survival following partial hepatectomy than TACE. Their postoperative prognosis could be accurately predicted by our proposed nomogram.

Intramedullary Nailing Combined with Bone Grafting for Benign Lesions of the Proximal Femur.

OBJECTIVE: To evaluate the effectiveness of intramedullary nailing for benign lesions of the proximal femur. METHOD: A retrospective analysis was carried out on 68 cases of benign lesions in the proximal femur at our hospital from April 2002 to April 2013 (38 men and 30 women). Mean age at surgery was 35.5 years (range, 22-56 years). The cases were divided into two groups: curettage of the lesion with bone grafting only as the grafting group (32 cases) and internal fixation after removal of the lesion as the fixation group (36 cases). For the grafting group, lesions were scraped out, deactivated and washed thoroughly with normal saline, then the allogeneic bone was implanted. For the fixation group, after the lesions were scraped, the intramedullary nails were implanted, and allogeneic bone was implanted into the scraped cavity with compaction. RESULTS: Pathological examination showed that 24 out of 68 cases (35.3%) had simple bone cysts (suffered from pathological fracture in 2 cases); 21 (30.9%) fibrous dysplasia; 18 (26.5%) aneurysmal bone cysts; 3 (4.4%) chondroblastoma, 2 (2.9%) out of which were combined with aneurysmal bone cysts. All patients were followed up for 12-96 months (56 months for mean). In the grafting group, 4 patients had postoperative complications (1 pathological bone fractures and 3 deep vein thrombosis), but only 1 patient of the fixation group (deep vein thrombosis) (P < 0.05). The average bedridden time after surgery was 11.4 ± 7.6 days for the grafting group, and for the other group was 7.5 ± 5.4 days ( P < 0.05). CONCLUSION: Both treatments are effective for benign lesions in the proximal femur, but the fixation group facilitated the functional recovery of patients and reduced postoperative complications.

A Randomized Controlled Study to Observe the Efficacy of External Treatment With a Traditional Chinese Medicine Herbal Ointment on Malignant Plural Effusion: Outcome Report and Design Review.

BACKGROUND: Malignant pleural effusion (MPE) is a common complication in most malignancies. Despite its frequent occurrence, current knowledge of MPE remains limited and the effect of the management is still unsatisfying. Traditional Chinese medicine (TCM) external treatment has unique advantages, such as quicker efficacy and fewer side effects. OBJECTIVE: To observe the effects and safety of Kang'ai Xiaoshui ointment (TCM herbal ointment) in MPE. DESIGN: This was a placebo-controlled double-blinded randomized study. A total of 80 patients were enrolled, of which 72 were randomized to receive Kang'ai Xiaoshui ointment or placebo at an allocation ratio of 1:1. Kang'ai Xiaoshui ointment or placebo was applied on the thorax wall for 8 hours daily. The intervention lasted 2 weeks. Kang'ai Xiaoshui ointment consisted of Astragalus membranaces （）, Semen pharbitidis （）, Cassia twig （）, Pericarpium arecae （）, Curcuma zedoary （）, Borneol （), and other substances. In both groups, diuresis and drainages were used as needed. Outcomes covered the quantity of pleural effusion evaluation, TCM Symptom Scale, Karnofsky Performance Scale, and safety indicators such as routine blood test, blood biochemistry test, and response table of skin irritation. RESULTS: Of 72 patients randomized to receive Kang'ai Xiaoshui ointment or placebo along with symptomatic treatment, the response rate was documented as 42.4% for the treatment group and 25.0% for the placebo group ( P = .138). As for the TCM symptom scale, the treatment group showed improvement in chest distress ( P = .003), fullness and distention ( P = .042), shortness of breath ( P < .001), no statistical significance in palpitation ( P = .237), and pain ( P = .063), whereas the placebo group did not show statistical significance in any of the 5 symptoms. Major adverse events related to the treatment, mainly skin irritation, were distributed equally. CONCLUSIONS: Kang'ai Xiaoshui ointment showed a potential of reducing MPE, and it could alleviate symptoms of dyspnea. Thus, it may be appropriate as a supplementary intervention for MPE. There were some flaws in the study design. A larger scale and better designed trial is advocated.

Research on Ground-Based LWIR Hyperspectral Imaging Remote Gas Detection.

The new progress of ground-based long-wave infrared remote sensing is presented, which describes the windowing spatial and temporal modulation Fourier spectroscopy imaging in details. The prototype forms the interference fringes based on the corner-cube of spatial modulation of Michelson interferometer, using cooled long-wave infrared photovoltaic staring FPA (focal plane array) detector. The LWIR hyperspectral imaging is achieved by the process of collection, reorganization, correction, apodization, FFT etc. from data cube. Noise equivalent spectral radiance (NESR), which is the sensitivity index of CHIPED-1 LWIR hyperspectral imaging prototype, can reach 5.6 x 10⁻8 W · (cm⁻¹ · sr · cm²)⁻¹ at single sampling. The data is the same as commercial temporal modulation hyperspectral imaging spectrometer. It can prove the advantage of this technique. This technique still has space to be improved. For instance, spectral response range of CHIPED-1 LWIR hyperspectral imaging prototype can reach 11. 5 µm by testing the transmission curve of polypropylene film. In this article, choosing the results of outdoor high-rise and diethyl ether gas experiment as an example, the authors research on the detecting method of 2D distribution chemical gas VOC by infrared hyperspectral imaging. There is no observed diethyl ether gas from the infrared spectral slice of the same wave number in complicated background and low concentration. By doing the difference spectrum, the authors can see the space distribution of diethyl ether gas clearly. Hyperspectral imaging is used in the field of organic gas VOC infrared detection. Relative to wide band infrared imaging, it has some advantages. Such as, it has high sensitivity, the strong anti-interference ability, identify the variety, and so on.

NOTUM is a potential pharmacodynamic biomarker of Wnt pathway inhibition.

Activation of Wnt signaling due to Wnt overexpression or mutations of Wnt pathway components is associated with various cancers. Blocking Wnt secretion by inhibiting PORCN enzymatic activity has shown efficacy in a subset of cancers with elevated Wnt signaling. Predicting response to upstream Wnt inhibitors and monitoring response to therapeutics is challenging due to the paucity of well-defined biomarkers. In this study we identify Notum as a potential biomarker for Wnt driven cancers and show that coordinate regulation of NOTUM and AXIN2 expression may be a useful predictor of response to PORCN inhibitors. Most importantly, as NOTUM is a secreted protein and its levels in blood correlate with tumor growth, it has potential as a pharmacodynamic biomarker for PORCN and other Wnt pathway inhibitors.

[The Endemic Situation and Challenges of Major Parasitic Diseases in China].

During the twelfth "Five-year Plan" period, the Chinese government further strengthened the implementation of several medium and long-term plans on disease control, which resulted in the acceleration of the control of schistosomiasis, malaria and echinococcosis. To further elucidate the endemic status and control experience during the stage, this article described current situation on the major parasitic diseases and put forward the challenges and consequent countermeasures for planning the control programs in the next five years and laying a foundation for the next Five-year Planning.

Effects of shark cartilage polysaccharides on the secretion of IL-6 and IL-12 in rheumatoid arthritis.

CONTEXT: Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by inflammation of the synovial membrane, leading to articular cartilage destruction. Shark cartilage polysaccharide (SCP) is a biodegradable, biocompatible, nontoxic, non-immunogenic and non-inflammatory polysaccharide that may be used in treating RA. OBJECTIVE: The anti-RA activities of SCP given orally to rats are investigated here for the first time. MATERIALS AND METHODS: SCP treatment group were administered with SCP-1, SCP-2 in the dosage of 9 mg/day for 24 days. The effect of SCP-1 and SCP-2 on the body weight, paw swelling, morphological changes of ankle and IL-6, IL-12 secretion in RA rats are examined. RESULTS: On day 24, there were no obvious differences in BMI between positive, SCP-1 and SCP-2 group. The swelling degree of SCP-1 and SCP-2 group was less serious than model group. X-ray revealed that SCP-1, SCP-2 group owned normal joint alignment and more smooth and tidy articular surface. The SCP-1 and SCP-2 have inhibitory effect on IL-6 (430.3 ± 25.6 pg/mL, 439.1 ± 35.9 pg/mL) and IL-12 (63.9 ± 20.1 pg/mL, 64.9 ± 14.1 pg/mL) secretion, which showed significant differences with model group (612 ± 72.3 pg/mL, 230.1 ± 29.2 pg/mL), but still higher than normal group (361.8 ± 47.1 pg/mL, 34.2 ± 15.1 pg/mL) and lower than positive group (418.1 ± 42.5 pg/mL, 90.2 ± 17.8 pg/mL). Especially, when the concentration of SCP was 125 µg/mL, the contents of IL-6 (431.1 ± 43.3 pg/mL, 401.7 ± 55.7 pg/mL) and IL-12 (63.2 ± 12.3 pg/mL, 52.3 ± 8.7 pg/mL) were lowest. DISCUSSION AND CONCLUSION: These findings demonstrate that SCP have excellent anti-RA activities and thus have great potential as a drug for treating RA diseases.

TP53 genomic status regulates sensitivity of gastric cancer cells to the histone methylation inhibitor 3-deazaneplanocin A (DZNep).

PURPOSE: DZNep (3-deazaneplanocin A) depletes EZH2, a critical component of polycomb repressive complex 2 (PRC2), which is frequently deregulated in cancer. Despite exhibiting promising anticancer activity, the specific genetic determinants underlying DZNep responsiveness in cancer cells remain largely unknown. We sought to determine molecular factors influencing DZNep response in gastric cancer. EXPERIMENTAL DESIGN: Phenotypic effects of DZNep were evaluated in a panel of gastric cancer cell lines. Sensitive lines were molecularly interrogated to identify potential predictors of DZNep responsiveness. The functional importance of candidate predictors was evaluated using short hairpin RNA (shRNA) and siRNA technologies. RESULTS: DZNep depleted PRC2 pathway components in almost all gastric cancer lines, however, only a subset of lines exhibited growth inhibition upon treatment. TP53 genomic status was significantly associated with DZNep cellular responsiveness, with TP53 wild-type (WT) lines being more sensitive (P < 0.001). In TP53-WT lines, DZNep stabilized p53 by reducing ubiquitin conjugation through USP10 upregulation, resulting in activation of canonical p53 target genes. TP53 knockdown in TP53-WT lines attenuated DZNep sensitivity and p53 target activation, showing the functional importance of an intact p53 pathway in regulating DZNep cellular sensitivity. In primary human gastric cancers, EZH2 expression was negatively correlated with p53 pathway activation, suggesting that higher levels of EZH2 may repress p53 activity. CONCLUSION: Our results highlight an important role for TP53 genomic status in influencing DZNep response in gastric cancer. Clinical trials evaluating EZH2-targeting agents such as DZNep should consider stratifying patients with gastric cancer by their TP53 genomic status.

[The current situation of blood pressure control and the influencing factors on hypertensive patients in residential communities of China].

OBJECTIVE: To understand the situation of blood pressure control and the major factors influencing the programs among those hypertensive patients living in the communities from different parts of China. METHODS: A protocol of community-based standardized blood pressure management was developed based on the current Chinese guideline for prevention, treatment of hypertension. Grass-roots caretakers from community health service centers across China were trained under the requirement of this protocol to manage the hypertensive patients. In this study, the hypertensive patients who had been registered in the project centers from Beijing, Hebei, Gansu, Jiangsu, Zhejiang, Guangdong provinces, were selected as the study subjects, and the baseline data for these patients was analyzed. RESULTS: By the end of 2010, a total of 242 182 patients were registered. The mean age was 61.0 ± 10.5, with 48.5% of them being males. The overall control rate of blood pressure was 27.4%. The control rate was significant lower among patients who were in lower age group, being male, with higher BMI, smoking, drinking or with more salt consumption. However, the control rate was significant higher among those patients who had family history of hypertension, always undertook physical exercise or receiving medical treatment. CONCLUSION: The blood pressure control rate for community hypertensive patients in China was still in a relatively low level. Standardization management measures should be strengthened so as to improve the rate of control on high blood pressure.

Value of contrast-enhanced intraoperative ultrasound for cirrhotic patients with hepatocellular carcinoma: a report of 20 cases.

AIM: To assess the clinical value of contrast-enhanced intraoperative ultrasound (CE-IOUS) as a novel tool in partial hepatectomy for cirrhotic patients with hepatocellular carcinoma (HCC). METHODS: From January 2007 to September 2007, a total of 20 consecutive cirrhotic patients with HCC scheduled to undergo partial hepatectomy were studied. Preoperative contrast enhanced computer tomography (CT) and/or magnetic resonance (MR) scans were performed within 1-2 wk before operation. Intraoperative ultrasound (IOUS) and CE-IOUS were carried out after mobilization of the liver. Lesions on precontrast and postcontrast scans were counted and mapped. CE-IOUS was performed with intravenous injection of ultrasound contrast agents SonoVue (Bracco Imaging, Milan, Italy). Arterial, portal and late phases of contrast enhancement were recorded and analyzed. Nodules showing arterial phase hyper-enhancing and/or hypo-enhancing in late parenchymal phase were considered malignant and removed surgically. Ultrasound-guided biopsy and ethanol ablation would be an option if the nodule could not be removed surgically. Newly detected nodules on IOUS showing iso-enhancement in both arterial and late phases were considered benign. These nodules were either removed surgically if they were close to the main lesion or followed by examinations of alpha-fetoprotein (AFP) level and ultrasound and/or CT/MR every 3 mo. RESULTS: IOUS found 41 nodules in total, among which 17 (41.46%) were newly detected compared to preoperative imaging. Thirty-three nodules were diagnosed malignant by CE-IOUS, including one missed by IOUS. The sensitivity and specificity of CE-IOUS on detecting HCC nodules are 100% (33/33 and 100% (9/9), respectively. Nine nodules were considered benign by CE-IOUS, four was confirmed at histology and five by follow-up. CE-IOUS changed the surgical strategy in 35% (7/20) of patients and avoid unnecessary intervention in 30% (6/20) of patients. CONCLUSION: CE-IOUS is a useful means to characterize the nodules detected by IOUS in cirrhotic liver, to find isoechoic HCC nodules which can not be shown on IOUS and to improve the accuracy of conventional IOUS, thus it can be used as an essential tool in the surgical treatment of cirrhotic patients with HCC.

Antioxidant stress is promoted by nano-anatase in spinach chloroplasts under UV-B radiation.

A proven photocatalyst, titanium dioxide in the form of nano-anatase, is capable of undergoing electron transfer reactions under light. In previous studies, we had proven that nano-anatase could absorb ultraviolet light (UV-B) and convert light energy to stable chemistry energy finally via electron transport in spinach chloroplasts. The mechanisms by which nano-anatase promotes antioxidant stress in spinach chloroplasts under UV-B radiation are still not clearly understood. In the present paper, we investigate the effects of nano-anatase on the antioxidant stress in spinach chloroplasts under UV-B radiation. The results showed that nano-anatase treatment could significantly decrease accumulation of superoxide radicals O2.-, hydrogen peroxide (H2O2), and malonyldialdehyde (MDA) content, and increase activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), and elevate evolution oxygen rate in spinach chloroplasts under UV-B radiation. Together, nano-anatase could decrease the oxidative stress to spinach chloroplast caused by UV-B radiation.