GDF-15 is a potential candidate biomarker for an elevated risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy.

Objective: Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine that regulates myocardial injury, cardiac overloading pressure, and inflammation and is related to the risk of cardiovascular diseases and events. The current study aimed to investigate the correlation of GDF-15 levels with clinical features, biochemical indices, and especially the risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy. Methods: A total of 103 HER2-positive breast cancer patients who underwent neoadjuvant dual anti-HER2 therapy (trastuzumab and pertuzumab plus chemotherapy) were included. Serum GDF-15 levels before neoadjuvant treatment were detected by enzyme-linked immunosorbent assay. Cardiotoxicity was evaluated during neoadjuvant therapy by referring to a decline of ≥10 percentage points in the left ventricular ejection fraction from baseline to an absolute level less than 50%. Results: GDF-15 exhibited a skewed distribution, with a median level of 714 (range: 207-1805) pg/mL. GDF-15 was positively correlated with age (p = 0.037), diabetes (p = 0.036), and the N-terminal pro-brain natriuretic peptide level (p = 0.013) and positively correlated with the total cholesterol level (p = 0.086) and troponin T level (p = 0.082), but these correlations were not statistically significant. A total of 6.8% of patients experienced cardiotoxicity during neoadjuvant therapy. By comparison, the GDF-15 level was greater in patients who experienced cardiotoxicity than in those who did not (p = 0.008). A subsequent receiver operating characteristic curve revealed that GDF-15 predicted cardiotoxicity risk, with an area under the curve of 0.803 (95% CI: 0.664-0.939). After multivariate adjustment, GDF-15 independently predicted a greater risk of cardiotoxicity (p = 0.020). Conclusion: GDF-15 is a candidate biomarker for increased risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy.

Application of artificial intelligence in ultrasound imaging for predicting lymph node metastasis in breast cancer: A meta-analysis.

BACKGROUND: This study aims to comprehensively evaluate the accuracy and effectiveness of ultrasound imaging based on artificial intelligence algorithms in predicting lymph node metastasis in breast cancer patients through a meta-analysis. METHODS: We systematically searched PubMed, Embase, and Cochrane Library for literature published up to May 2023. The search terms included artificial intelligence, ultrasound, breast cancer, and lymph node. Studies meeting the inclusion criteria were selected, and data were extracted for analysis. The main evaluation indicators included sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the curve (AUC). The heterogeneity was assessed using the Cochrane Q test combined with the I^2 statistic expressing the percentage of total effect variation that can be attributed to the effect variation between studies, as recommended by the Cochrane Handbook for heterogeneity quantification. A threshold p-value of 0.10 was considered to compensate for the low power of the Q test. Sensitivity analysis was performed to assess the stability of individual studies, and publication bias was determined with funnel plots. Additionally, fagan plots were used to assess clinical utility. RESULTS: Ten studies involving 4726 breast cancer patients were included in the meta-analysis. The results showed that ultrasound imaging based on artificial intelligence algorithms had high accuracy and effectiveness in predicting lymph node metastasis in breast cancer patients. The pooled sensitivity was 0.88 (95% CI: 0.81-0.93; P < 0.001; I2 = 84.68), specificity was 0.75 (95% CI: 0.66-0.83; P < 0.001; I2 = 91.11), and AUC was 0.89 (95% CI: 0.86-0.91). The positive likelihood ratio was 3.5 (95% CI: 2.6-4.8), negative likelihood ratio was 0.16 (95% CI: 0.10-0.26), and diagnostic odds ratio was 23 (95% CI: 13-40). However, the combined sensitivity of ultrasound imaging based on non-AI algorithms for predicting lymph node metastasis in breast cancer patients was 0.78 (95%CI: 0.63-0.88), the specificity was 0.76 (95%CI: 0.63-0.86), and the AUC was 0.84 (95%CI: 0.80-0.87). The positive likelihood ratio was 3.3 (95% CI: 1.9-5.6), the negative likelihood ratio was 0.29 (95% CI: 0.15-0.54), and the diagnostic odds ratio was 11 (95% CI: 4-33). Due to limited sample size (n = 2), meta-analysis was not conducted for the outcome of predicting lymph node metastasis burden. CONCLUSION: Ultrasound imaging based on artificial intelligence algorithms holds promise in predicting lymph node metastasis in breast cancer patients, demonstrating high accuracy and effectiveness. The application of this technology helps in the diagnosis and treatment decisions for breast cancer patients and is expected to become an important tool in future clinical practice.

IL-27-induced, MSC-derived Exosomes Promote MMP3 Expression Through the miR-206/L3MBTL4 Axis in Synovial Fibroblasts.

Context: In rheumatoid arthritis (RA), hyperproliferative fibroblast-like synoviocytes (FLS) can secrete a variety of tissue hydrolases, such as matrix metalloproteinases (MMPs), causing the destruction of chondrocytes. Mesenchymal stem cells (MSCs) can directly affect FLS through extracellular vesicles (EVs). Interleukin-27 (IL-27) is a pleiotropic immune regulator frequently overexpressed in RA. Objective: The study intended to examine the effects of IL-27-induced exosomes from bone-marrow mesenchymal stem cells (BM-MSCs) and to determine if they promote the secretion of MMP3 in synovial cells. Design: The research team performed a genetic study. Setting: The study took place at the First Affiliated Hospital of Hainan Medical University in Haikou City, Hainan, China. Outcome Measures: The research team: (1) determined if IL-27 expression had occurred in the synovial fluid; (2) co-cultured IL-27-induced MSCs with FLS to detect the expression of MMP3 in the FLS; (3) Under IL-27 induction, MSC-derived exosomes with IL-27R knockdown were collected to detect the expression of microRNAs(miRNAs) associated with RA; (4) screened the miRNAs to determine the most significant differences in expression; (5) determined the miRNA target genes in arthritis, using Western blot (WB) and qRT-PCR; and (6) Dual luciferase and ChIP experiments confirm regulation of MMP3 by L3MBTL4. Results: IL-27 was highly expressed in RA, and the IL-27-induced, MSC-derived exosomes promoted the expression of MMP3 in FLS. The IL-27-induced MSC-derived exosomes significantly upregulated the expression of miR-206-3p, and the miR-206-3p target, miR-206/ lethal(3) malignant brain tumor-like protein 4 (L3MBTL4), regulated the MMP3 transcription. The IL-27-induced, MSC-derived exosomes promoted MMP3 expression in the FLS through the miR-206-3p/L3MBTL4 axis, thereby promoting chondrocyte degradation and aggravating RA. Conclusions: IL-27 can induce the expression of miR-206 in MSCs, and miR-206 can be transported into FLS through MSC-EVs to promote FLS migration and MMP3 expression and aggravate articular cartilage damage. Patients with RA who have a high IL-27 expression may not be suitable to receive treatment with MSCs, and clinicians can use MSCs that knock down or delete IL-27R to treat RA patients who have a high IL-27 expression.

Efficacy and safety of neoadjuvant pyrotinib plus docetaxel/liposomal doxorubicin/cyclophosphamide for HER2-positive breast cancer.

OBJECTIVE: Pyrotinib is a novel EGFR/HER2 dual tyrosine kinase inhibitor developed in China, while its role in neoadjuvant therapy of HER2-positive (HER2+) breast cancer lacks evidence. The current study aimed to explore the efficacy and safety of neoadjuvant pyrotinib plus docetaxel/liposomal doxorubicin/cyclophosphamide (TAC) for HER2+ breast cancer. METHODS: A total of 27 HER2+ breast cancer patients received neoadjuvant pyrotinib plus TAC for 6 cycles, then surgery was performed. The clinical and pathological responses, and adverse events were evaluated. RESULTS: Complete response rate, objective response rate, and disease control rate were 0.0%, 44.4% and 100.0% after 2 treatment cycles; 0.0%, 37.0%, and 100.0% after 4 treatment cycles; 37.0%, 37.0%, and 96.3% after 6 treatment cycles; as well as 37.0%, 44.4%, and 100.0% based on the best clinical response. Regarding pathological response, there were 1 (2.7%), 3 (11.1%), 8 (29.6%), 5 (18.5%), and 10 (37.0%) patients realizing Miller-Payne grade (G) 1, G2, G3, G4, and G5, respectively; besides, 10 (37.0%) patients achieved total pathological complete response (pCR), 10 (37.0%) patients realized pCR in breast, and 23 (85.2%) patients achieved pCR in lymph node. Additionally, adverse events included diarrhea (81.5%), dental ulcer (7.4%), and hand-foot syndrome (3.7%); meanwhile, grade 3-4 adverse event consisted of only diarrhea (11.1%). CONCLUSION: Neoadjuvant pyrotinib plus TAC treatment is efficient and safe in HER2+ breast cancer patients, while further validation is needed.

MiR-135a-5p suppresses breast cancer cell proliferation, migration, and invasion by regulating BAG3.

BACKGROUND: MicroRNAs (miRNAs) are involved in the progression of diverse human cancers. This work aimed to delve into how microRNA-135a-5p (miR-135a-5p) affects the biological behaviors of Breast Cancer (BC) cells. METHODS: Gene Expression Omnibus (GEO) datasets were used to analyze the expression differences of miR-135a-5p in cancer tissues of BC patients. Quantitative real-time PCR and western blot were conducted to detect miR-135a-5p and Bcl-2 Associated Athanogene (BAG3) expression levels in BC tissues and cells, respectively. The proliferation, migration, invasion, and cell cycle of BC cells were detected by cell counting kit-8 assay, BrdU assay, wound healing assay, transwell assay, and flow cytometry. The targeted relationship between miR-135a-5p and BAG3 mRNA 3'UTR predicted by bioinformatics was further testified by a dual-luciferase reporter gene assay. Pearson's correlation analysis was adopted to analyze the correlation between miR-135a-5p expression and BAG3 expression. The downstream pathways of BAG3 were analyzed by the LinkedOmics database. RESULTS: MiR-135a-5p was significantly down-regulated and BAG3 expression was significantly raised in BC tissues. MiR-135a-5p overexpression repressed the viability, migration and invasion of BC cells, and blocked cell cycle progression in G0/G1 phase while inhibiting miR-135a-5p worked oppositely. BAG3 was verified as a target of miR-135a-5p. Overexpression of BAG3 reversed the impacts of miR-135a-5p on the malignant biological behaviors of BC cells. The high expression of BAG3 was associated with the activation of the cell cycle, mTOR and TGF-ß signaling pathways. CONCLUSION: MiR-135a-5p regulates BAG3 to repress the growth, migration, invasion, and cell cycle progression of BC cells.

[Antitumor Effect of Dihydroartemisinin on Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the potential antitumor effect and its mechanism of dihydroartemisinin (DHA) on diffuse large B-cell lymphoma (DLBCL). METHODS: OCI-Ly7 cells were respectively treated with different concentrations of DHA (0, 12.5, 25, 50 and 100 µmol/L) , CCK-8 was used to detect the cells viability. Subsequently, OCI-Ly7 cells were divided into 5 groups : DHA 0,25,50,100 µmol / L and DHA (100 µmol / L) + Colivelin (STAT3 activator). Aldehyde dehydrogenase (ALDH) positive cells were sorted by flow cytometry, the sphere-forming ability of stem cells was detected. Transwell assay and scratch test were used to analyze the invasion and migration of cells. Western blot was used to detect the expression of migration and invasion-related proteins, as well as the phosphorylation levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3(STAT3). RESULTS: DHA induced obvious cytotoxicity to OCI-Ly7 cells. Compared with the control group, the stem cell-like properties, invasion and migration of OCI-Ly7 were significantly inhibited in DHA 50 µmol/L group and 100 µmol/L group, while the phosphorylation levels of JAK2 and STAT3 were significantly reduced. There was no significant difference in DHA 25 µmol/L group compared with the control group. Treated with Colivelin, the inhibition of DHA on OCI-Ly7 stem cell-like properties, invasion and migration was significantly reversed, and the expression of p-STAT3 was significantly up-regulated. CONCLUSION: DHA has antitumor effect on DLBCL, and its mechanism may be through inhibiting the activation of JAK2/STAT3 pathway to inhibit the stem cell-like properties, invasion and migration of DLBCL cells.

IL-33/ST2 Activation Is involved in Ro60-Regulated Photosensitivity in Cutaneous Lupus Erythematosus.

Interleukin- (IL-) 33 contributes to various inflammatory processes. IL-33/ST2 activation participates in systemic lupus erythematous via binding to the receptor of Suppression of Tumorigenicity 2 protein (ST2). However, whether IL-33/ST2 interferes with the nosogenesis of cutaneous lupus erythematosus (CLE) has not been reported so far. Herein, we proposed to disclose the impacts on IL-33/ST2 activation and Ro60 on CLE and their potential implications in the photosensitization of CLE cells. IL-33, ST2, and Ro60 in CLE patients' skin lesions were detected. Murine keratinocytes stimulated with or without IL-33 were irradiated by ultraviolet B (UVB), and the levels of Ro60 and inflammation markers were determined. Keratinocytes were cocultured with J774.2 macrophages and stimulated with IL-33 for analysis of chemostasis. The results identified that IL-33, ST2, and downstream inflammation markers were significantly upregulated in CLE lesions with Ro60 overexpression. Additionally, IL-33 treatment promoted the upregulation of Ro60 induced by UVB treatment in murine keratinocytes. Moreover, IL-33 stimulates keratinocytes to induce macrophage migration via enhancing the generation of the chemokine (C-C motif) ligands 17 and 22. Meanwhile, the silencing of ST2 or nuclear factor-kappa B (NF-κB) suppression abolished IL-33-induced upregulation of Ro60 in keratinocytes. Similarly, the inhibition of SOX17 expression was followed by downregulation of Ro60 in keratinocytes following IL-33 stimulation. In addition, UVB irradiation upregulated SOX17 in keratinocytes. Conclusively, the IL-33/ST2 axis interferes with Ro60-regulated photosensitization via activating the NF-κB- and PI3K/Akt- and SOX17-related pathways.

Correlation of TBK1, AR, and other serum cancer-related biomarkers in breast cancer patients: An observational study.

Breast cancer (BC) ranks first for incidence and mortality in gynecological malignant tumors. This study aims to investigate the diagnostic value of Tank-binding kinase 1 (TBK1) and its correlation with androgen receptor (AR) and other serum cancer-related biomarkers in BC patient. The present observational study included 451 female BC patients and 451 healthy controls. Serum levels of TBK1, AR and other cancer-related biomarkers were detected in all the patients and healthy controls. Patients' demographic data and clinical data including age, body mass index (BMI), tumor node Metastasis (TNM), pathological type, tumor size and lymph node metastasis were collected. The follow-up lasted for 5 years. The deceased group had higher rate of patients with TNM III~IV, lymph node metastasis or tumor diameter >2. Deceased group had much higher rate of patients with negative ER and positive Ki67. Besides, increased TBK1 was found in BC patients with positive correlation with AR, CA15-3, CA125, CEA, and CA19-9. Serum TBK1 was associated with the clinic outcomes of BC patients and those with high TBK1 had lower 5-year survival rate. Moreover, cutoff value of 13.95 ng/mL TBK1 showed AUC of 0.981 (93.6% for sensitivity and 86.3% for specificity) for diagnosing BC, and cutoff value of 22.65 ng/mL TBK1 had AUC of 0.996 (97.7% for sensitivity and 96.3% for specificity) for diagnosing the death of BC patients. Serum TBK1 was positively correlated with AR and other serum cancer-related biomarkers. In addition, high TBK1 predicted the poor prognosis and might be used for the diagnosis of BC.

Deficit drip irrigation based on crop evapotranspiration and precipitation forecast improves water- use efficiency and grain yield of summer maize.

BACKGROUND: Limited and erratic precipitation with inefficient irrigation scheduling often leads to an unstable crop yield and low water-use efficiency (WUE) in semi-arid and semi-humid regions. A 2-year field experiment was conducted to evaluate the effect of three irrigation strategies (conventional irrigation (CK), full-drip irrigation (FI), based on crop evapotranspiration and precipitation forecast, and deficit drip irrigation (DI) (75% FI)) on photosynthetic characteristics, leaf-to-air temperature difference (∆T), grain yield, and the WUE of summer maize. RESULTS: The results showed that the daily average net photosynthetic rate (Pn) of DI and FI increased by 25.4% and 25.8% at jointing stage in 2018, and 26.3% and 26.5% at grain-filling stage in 2019 compared with CK, respectively. At jointing stage in 2018 and grain-filling stage in 2019, the transpiration rate (Tr) of DI was significantly lower than that of FI (P < 0.05) but there was insignificant difference in Pn value (P > 0.05). The ∆T between 12:00-14:00 of DI and FI was significantly lower than that of CK at jointing stage in 2018 and grain-filling stage in 2019 (P < 0.05). The 2-year average grain yields of DI and FI were 11.4 and 11.5 t ha-1 , which increased by 32.4% and 32.8% compared with CK, respectively. The WUE of DI was 2.82 kg m-3 , which was 17.9% and 33.8% higher than that of FI and CK, respectively. CONCLUSION: Deficit drip irrigation based on crop evapotranspiration and precipitation forecast improves crop WUE and maintains high grain yields in semi-arid and semi-humid regions. © 2021 Society of Chemical Industry.

MiR-135a-5p suppresses breast cancer cell proliferation, migration, and invasion by regulating BAG3

Abstract Background MicroRNAs (miRNAs) are involved in the progression of diverse human cancers. This work aimed to delve into how microRNA-135a-5p (miR-135a-5p) affects the biological behaviors of Breast Cancer (BC) cells. Methods Gene Expression Omnibus (GEO) datasets were used to analyze the expression differences of miR-135a-5p in cancer tissues of BC patients. Quantitative real-time PCR and western blot were conducted to detect miR-135a-5p and Bcl-2 Associated Athanogene (BAG3) expression levels in BC tissues and cells, respectively. The proliferation, migration, invasion, and cell cycle of BC cells were detected by cell counting kit-8 assay, BrdU assay, wound healing assay, transwell assay, and flow cytometry. The targeted relationship between miR-135a-5p and BAG3 mRNA 3′UTR predicted by bioinformatics was further testified by a dual-luciferase reporter gene assay. Pearson's correlation analysis was adopted to analyze the correlation between miR-135a-5p expression and BAG3 expression. The downstream pathways of BAG3 were analyzed by the LinkedOmics database. Results MiR-135a-5p was significantly down-regulated and BAG3 expression was significantly raised in BC tissues. MiR-135a-5p overexpression repressed the viability, migration and invasion of BC cells, and blocked cell cycle progression in G0/G1 phase while inhibiting miR-135a-5p worked oppositely. BAG3 was verified as a target of miR-135a-5p. Overexpression of BAG3 reversed the impacts of miR-135a-5p on the malignant biological behaviors of BC cells. The high expression of BAG3 was associated with the activation of the cell cycle, mTOR and TGF-β signaling pathways. Conclusion MiR-135a-5p regulates BAG3 to repress the growth, migration, invasion, and cell cycle progression of BC cells.

Ultrasound Image Features under Deep Learning in Breast Conservation Surgery for Breast Cancer.

This study was to analyze the effect of the combined application of deep learning technology and ultrasound imaging on the effect of breast-conserving surgery for breast cancer. A deep label distribution learning (LDL) model was designed, and the semiautomatic segmentation algorithm based on the region growing and active contour technology (RA) and the segmentation model based on optimized nearest neighbors (ON) were introduced for comparison. The designed algorithm was applied to the breast-conserving surgery of breast cancer patients. According to the difference in intraoperative guidance methods, 102 female patients with early breast cancer were divided into three groups: 34 cases in W1 group (ultrasound guidance based on deep learning segmentation model), 34 cases in W2 group (ultrasound guidance), and 34 cases in W3 group (palpation guidance). The results revealed that the tumor area segmented by the LDL algorithm constructed in this study was closer to the real tumor area; the segmentation accuracy (AC), Jaccard, and true-positive (TP) values of the LDL algorithm were obviously greater than those of the RA and ON algorithms, while the false-positive (FP) value was significantly lower in contrast to the RA and ON algorithms, showing statistically observable differences (P < 0.05); the actual resection volume of the patients in the W1 group was the closest to the ideal resection volume, which was much smaller in contrast to that of the patients in the W2 and W3 groups, showing statistical differences (P < 0.05); the positive margins of the patients in the W1 group were statistically lower than those in the W2 and W3 groups (P < 0.05). In addition, 1 patient in the W1 group was not satisfied with the cosmetic effect, 3 patients in the W2 group were not satisfied with the cosmetic effect, and 9 patients in the W3 group were not satisfied with the cosmetic effect. Finally, it was found that the ultrasound image based on the deep LDL model effectively improved the AC of tumor resection and negative margins, reduced the probability of normal tissue being removed, and improved the postoperative cosmetic effect of breast.

The complete chloroplast genome of Rhododendron platypodum (Ericaceae): an endemic and endangered species from China.

Rhododendron platypodum Diels (Ericaceae) is a Chinese endemic and endangered species with high ornamental value. Here the complete chloroplast (cp) genome of R. platypodum was assembled and characterized. The cp genome is in a total length of 201,047 bp with the typical quadripartite structure of angiosperms, containing two inverted repeats (IRs) of 44,650 bp separated by a large single-copy (LSC) region of 109,134 bp and a small single-copy (SSC) region of 2613 bp. The whole cp genome of R. platypodum contains 143 genes, including 93 protein-coding genes, 42 transfer RNA genes and 8 ribosomal RNA genes. Phylogenetic analysis based on the coding sequences of cp genome within the Ericaceae family suggests that R. platypodum is closely related to R. delavayi.

Forest management practices of Pinus tabulaeformis plantations alter soil organic carbon stability by adjusting microbial characteristics on the Loess Plateau of China.

Sustainable management practices can enhance the capacity and potential for soil carbon (C) sequestration, significantly contributing towards mitigating regional climate change. Here, we investigated how the microbial characteristics of a Pinus tabulaeformis plantation responded to different management practices to identify the role of microbial characteristics in influencing the stability of soil organic carbon (SOC). We chose a Pinus tabulaeformis plantation on the Loess Plateau where forest management practices had been conducted since 1999. Five forest management practices were implemented: two at the forest level (P. tabulaeformis with and without ground litter), and three using different vegetation restoration approaches after clear-cutting (P. tabulaeformis seedlings, abandoned grassland, and natural shrub regeneration). Microbial biomass, soil respiration, microbial community structure, microbial metabolic function, and soil oxidizable organic carbon (OC) fractions were evaluated. Forest management practices changed SOC stability by adjusting the microbial characteristics (e.g. soil microbial community diversity and microbial metabolic function diversity). The result of path analysis was that the direct path coefficient of microbial biomass on soil oxidizable OC fractions was the largest, which was 1.499. Path analysis and redundancy analysis showed that microbial biomass had the largest direct influence on soil oxidizable OC fractions. Compared with other forest management practices, natural shrub regeneration increased the nonlabile carbon fraction by increasing soil microbial characteristics, and contributed the most towards stabilizing SOC, which enhanced the stability of the soil ecosystem on the plateau. In conclusion, microbial biomass was the biggest influence factor of SOC stability. In contrast, the stability of SOC may be most stable in the area of natural shrub regeneration.

[Spatial-temporal trend of grassland net primary production and their driving factors in the Loess Plateau, China]. / é»„åœŸé«˜åŽŸè‰åœ°å‡€åˆçº§ç”Ÿäº§åŠ›æ—¶ç©ºè¶‹åŠ¿åŠå ¶é©±åŠ¨å› ç´ .

Net primary productivity (NPP) of grassland is a key link and important part of the ecosystem's carbon cycle. We estimated the changes of NPP in grasslands of the Loess Plateau with unchanged land use types during 2000-2015 and analyzed its responses to the variation of main climate factors (annual precipitation, annual heavy rainfall, annual effective rainfall days, annual average temperature, annual maximum temperature, annual minimum temperature) using piecewise linear regression and Pearson correlation analysis. The driving factors of grassland NPP were further analyzed by pixel-by-pixel with boosted regression tree analysis. The results showed that annual mean grassland NPP in the Loess Plateau showed an increasing trend during the study period, with 51.3% of the total grassland area showing a significant increasing trend. The average increase rate of annual mean NPP declined from 15.23 g C·m-2·a-1 in 2000-2004 to 3.58 g C·m-2·a-1 in 2004-2015. There was a significant positive correlation between grassland NPP and precipitation, but negative correlation with temperature factors. Annual precipitation was the dominant climatic factor affecting NPP of the whole study area with the highest relative importance. Annual maximum temperature was the dominant driving force of grassland NPP of central Loess Plateau, while annual minimum temperature mainly affected the growth of grassland in high-altitude area of the western Loess Plateau.

Anti-inflammatory effects of luteolin on acute gouty arthritis rats via TLR/MyD88/NF-κB pathway. / æœ¨çŠ€è‰ç´ é€šè¿‡TLR/MyD88/NF-κBé€šè·¯å‚ä¸Žæ€¥æ€§ç—›é£Žæ€§å ³èŠ‚ç‚Žå¤§é¼ çš„æŠ—ç‚Žä½œç”¨.

OBJECTIVES: To investigate the anti-inflammatory effect of luteolin on the acute gouty arthritis (AGA) rats and the underlying mechanisms. METHODS: A total of sixty rats were chosen and randomly divided into 5 groups:A control group, a monosodium urate (MSU) group, a colchicine group, 2 luteolin groups (50 mg/kg, 150 mg/kg). The AGA model of rats was established by injecting monosodium urate (MSU) at the concentration of 25 mg/mL into the ankle joint cavity. Changes of joint swelling index at different time points and the levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum and synovial were measured. The mRNA expression of TLR2, TLR4, and MyD88 in synovial tissue was detected by real-time PCR, and the protein expression of TLR2, TLR4, MyD88, and NF-κB in synovial tissues was determined by Western blotting. The inflammatory cells of the ankle joint and its surrounding soft tissues were observed after HE staining, and the expression of NF-κB was determined by immunohistochemistry. RESULTS: Compared with the MSU group, the joint swelling indexes of the luteolin group and the colchicine group were significantly decreased (P<0.05), and the levels of IL-1ß, IL-6 and TNF-α were also significantly decreased (P<0.01). The mRNA levels of TLR2, TLR4, and MyD88 and the protein levels of TLR2, TLR4, MyD88, and NF-κB were significantly decreased (P<0.01). CONCLUSIONS: Luteolin can reduce the inflammatory response of acute gouty arthritis via down-regulating the TLR/MyD88/NF-κB pathway, and it is expected to be an effective drug for the treatment of acute gouty arthritis.

Association of plasma apolipoprotein CIII, high sensitivity C-reactive protein and tumor necrosis factor-α contributes to the clinical features of coronary heart disease in Li and Han ethnic groups in China.

BACKGROUND: Apolipoprotein CIII (apoCIII) is an independent risk for coronary heart disease (CHD). In this study, we investigated the associations among plasma apoCIII, hs-CRP and TNF-α levels and their roles in the clinical features of CHD in the Li and Han ethnic groups in China. METHODS: A cohort of 474 participants was recruited (238 atherosclerotic patients and 236 healthy controls) from the Li and Han ethnic groups. Blood samples were obtained to evaluate apoCIII, TNF-α, hs-CRP and lipid profiles. Chi-squared, t-tests, and Kruskal-Wallis or Wilcoxon-Mann-Whitney tests, Pearson or Spearman correlation tests and multiple unconditional logistic regression were employed to analyze lipid profiles and variations in plasma apoCIII, TNF-α, hs-CRP in subgroups of CHD and their contributions to CHD using SPSS version 20.0 software. RESULTS: Compared to healthy participants, unfavorable lipid profiles were identified in CHD patients with enhanced systolic pressure, diastolic pressure, fasting blood sugar (FBS), TG, TC, LDL-C, apoB, Lp(a) (P < 0.05, TC and Lp(a); P < 0.01, FBS, TG, LDL-C, apoB); and lower HDL-C and apoAI (P < 0.05). Plasma apoCIII, TNF-α and hs-CRP levels were higher in CHD individuals (16.77 ± 5.98 mg/dL vs. 10.91 ± 4.97 mg/dL; 17.23 ± 6.34 pg/mL vs. 9.49 ± 3.88 pg/mL; 9.55 ± 7.32 mg/L vs. 2.14 ± 1.56 mg/L; P < 0.01 vs. healthy participants). Identical patterns were obtained in the Li and Han groups (16.46 ± 6.08 mg/dL vs. 11.72 ± 5.16 mg/dL; 15.71 ± 5.52 pg/mL vs. 9.74 ± 4.31 pg/mL; 8.21 ± 7.09 mg/L vs. 2.15 ± 1.51 mg/L in Li people; 17.05 ± 5.90 mg/dL vs. 10.07 ± 4.63 mg/dL; 18.59 ± 6.73 pg/mL vs. 9.23 ± 3.38 pg/mL; 10.75 ± 7.44 mg/L vs. 2.12 ± 1.63 mg/L in Han people; P < 0.01). Paired comparisons of subgroups with stable angina, unstable angina, and acute myocardial infarction (AMI) revealed significant variation in plasma levels of apoCIII, TNF-α and hs-CRP (P < 0.01), but not among subgroups with mild, moderate and severe stenosis (P > 0.05). Plasma apoCIII, TNF-α and hs-CRP contributed to the development of CHD (OR = 2.554, 7.252, 6.035, P < 0.01) with paired correlations in CHD patients (apoCIII vs. TNF-α, r = 0.425; apoCIII vs. hs-CRP, r = 0.319; TNF-α vs. hs-CRP, r = 0.400, P < 0.01). CONCLUSIONS: Association among plasma apoCIII, hs-CRP and TNF-α interacts with unfavorable lipid profiles to contribute to the clinical features of CHD with stable angina, unstable angina, and AMI in the Li and Han ethnic groups in China.

Association of the S2 allele of the SstI polymorphism in the apoC3 gene with plasma apoCIII interacts with unfavorable lipid profiles to contribute to atherosclerosis in the Li ethnic group in China.

BACKGROUND: The SstI polymorphism in the apolipoprotein 3 gene (apoC3) has been identified in many ethnic groups. In addition, the S2 allele of the SstI polymorphism is shown to be associated with increased plasma triglyceride (TG) levels. Plasma apoCIII is an important atherogenic factor, which interrupts lipid metabolism and is positively associated with plasma TG levels. However, the existence of the SstI polymorphism in the Li ethnic group in China remains to be confirmed. The relationship between the S2 allele of the SstI polymorphism and plasma apoCIII or TG and their roles in atherosclerosis are also unknown. METHODS: A cohort of 628 participants was recruited (316 atherosclerotic patients and 312 healthy controls) from both the Li and Han ethnic groups. Blood samples were obtained to evaluate the SstI polymorphism in the apoC3 and lipid profiles. Chi-squared and t-tests and multiple unconditional logistic regression were employed to analyze the genotypic and allelic frequencies and lipid profiles using SPSS version 20.0 software. RESULTS: The SstI polymorphism in the apoC3 was identified in the Li ethnic group. The S2 allele and plasma apoCIII and TG levels were associated with the development of atherosclerosis (P < 0.01, S2 allele and apoCIII; P < 0.05, TG) in the Li ethnic group. The S2 allele was associated with increased plasma apoCIII levels in the atherosclerotic group (P < 0.01), but with increased plasma apoCIII and TG levels in control group (both P < 0.01). In addition to the increases in the S2 allele frequency and plasma TG and apoCIII levels, atherosclerotic patients in the Li ethnic group also exhibited increased apoB, decreased HDL-C and apoAI and a lower apoAI:apoB ratio (all P < 0.01). CONCLUSIONS: Our results indicate that the S2 allele of the SstI polymorphism in the apoC3 gene is associated with plasma apoCIII levels in the Li population. In combination with unfavorable lipid profiles, this might contribute to susceptibility to atherosclerosis.

Seasonal variations in carbon, nitrogen and phosphorus concentrations and C:N:P stoichiometry in different organs of a Larix principis-rupprechtii Mayr. plantation in the Qinling Mountains, China.

Understanding how concentrations of elements and their stoichiometry change with plant growth and age is critical for predicting plant community responses to environmental change. We used long-term field experiments to explore how the leaf, stem and root carbon (C), nitrogen (N) and phosphorous (P) concentrations and their stoichiometry changed with growth and stand age in a L. principis-rupprechtii Mayr. plantation from 2012-2015 in the Qinling Mountains, China. Our results showed that the C, N and P concentrations and stoichiometric ratios in different tissues of larch stands were affected by stand age, organ type and sampling month and displayed multiple correlations with increased stand age in different growing seasons. Generally, leaf C and N concentrations were greatest in the fast-growing season, but leaf P concentrations were greatest in the early growing season. However, no clear seasonal tendencies in the stem and root C, N and P concentrations were observed with growth. In contrast to N and P, few differences were found in organ-specific C concentrations. Leaf N:P was greatest in the fast-growing season, while C:N and C:P were greatest in the late-growing season. No clear variations were observed in stem and root C:N, C:P and N:P throughout the entire growing season, but leaf N:P was less than 14, suggesting that the growth of larch stands was limited by N in our study region. Compared to global plant element concentrations and stoichiometry, the leaves of larch stands had higher C, P, C:N and C:P but lower N and N:P, and the roots had greater P and C:N but lower N, C:P and N:P. Our study provides baseline information for describing the changes in nutritional elements with plant growth, which will facilitates plantation forest management and restoration, and makes a valuable contribution to the global data pool on leaf nutrition and stoichiometry.

The organochlorine pesticides residues in the invasive ductal breast cancer patients.

Investigation of organochlorine pesticides residues (important environmental contamination causing malignant transformation) in breast cancer patients is valuable to understanding their roles in breast cancer. 75 invasive ductal carcinoma (IDC) patients were enrolled with control of 79 benign breast diseases patients and control of 80 healthy women. Morning fasting blood specimens and adipose tissue specimens beside the primary lesion were detected with gas chromatograph. In blood specimens, both levels of ß-HCH and PCTA were higher in IDC than those in both controls (both p<0.05), and increasingly higher among the three IDC degrees. In adipose tissue specimens, all levels of ß-HCH, PCTA and pp'-DDE were higher in IDC than those in control (all p<0.05) and increasingly higher among three IDC degrees. The levels of ß-HCH, PCTA in both blood specimens and adipose tissue specimens were higher in estrogen receptor (ER) positive IDC than those in ER negative IDC (all p<0.05). The higher level of organochlorine pesticides residues in blood and adipose tissue specimens of IDC infers its association with IDC, but the details remains to reveal, and this study may helpful in this field.

The allogeneic umbilical cord mesenchymal stem cells regulate the function of T helper 17 cells from patients with rheumatoid arthritis in an in vitro co-culture system.

BACKGROUND: Previous in vivo studies have shown that mesenchymal stem cell (MSC) transplantation significantly improves the condition of a number of autoimmune diseases including autoimmune cerebrospinal meningitis, multiple sclerosis, glomerulonephritis and systemic lupus erythematosus. METHODS: To investigate the immunoregulatory effect of stem cell transplantation, human umbilical cord MSCs were co-cultured with peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis (RA). Orphan nuclear receptor gamma (ROR-γ) mRNA and protein expression was detected with real-time PCR and Western blotting. Interleukin (IL)-17, IL-6 and tumor necrosis factor (TNF-α) in the cell culture supernatant were measured using a flow cytometric bead capture method. RESULTS: After 72 hours of co-culture, the mRNA and protein expression levels of ROR-γ in co-cultured PBMCs were decreased compared with that in PBMC of RA patients cultured alone (p < 0.05). Moreover, the decrement was positively related to the disease activity of RA (p < 0.05). Decreased secretion of IL-17, TNF-α and IL-6 were also found in co-culture supernatants of PBMCs from patients with severe and moderate disease activity, but not in supernatant from PBMCs cultured alone. The decreased cytokine expression levels were positively correlated to the concentrations of MSCs. In contrast, PBMCs from healthy controls or patients with mild RA did not show significant differences in ROR-γ expression or cytokine secretion following co-culture with MSCs as compared with those cultured alone. CONCLUSIONS: In vitro co-culture with MSCs down-regulated the inflammatory response of PBMCs from RA patients with severe disease activity, but had no significant effect on PBMCs from healthy controls or patients with mild disease activity, suggesting that the immunoregulatory role of MSCs may associate with the occurrence of inflammatory mediators.