Granulosa Cells-Related MicroRNAs in Ovarian Diseases: Mechanism, Facts and Perspectives.

MicroRNAs (miRNAs) are a class of short single-stranded, noncoding RNAs that affect the translation of mRNAs by imperfectly binding to homologous 3'UTRs. Research on miRNAs in ovarian diseases is constantly expanding because miRNAs are powerful regulators of gene expression and cellular processes and are promising biomarkers. miRNA mimics, miRNA inhibitors and molecules targeting miRNAs (antimiRs) have shown promise as novel therapeutic agents in preclinical development. Granulosa cells (GCs) are supporting cells for developing oocytes in the ovary. GCs regulate female reproductive health by producing sex hormones and LH receptors. Increasing research has reported the relevance of miRNAs in GC pathophysiology. With in-depth studies of disease mechanisms, there are an increasing number of studies on the biomolecular pathways of miRNAs in gynecology and endocrinology. In the present review, we summarize the different functions of GC-related microRNAs in various ovarian disorders, such as polycystic ovary syndrome, premature ovarian insufficiency, premature ovarian failure and ovarian granulosa cell tumors.

A Woman with Klippel-Trenaunay Syndrome Reproductive Tract Bleeding Case Report and Review of the Literature.

Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder characterized by wine stains, abnormal tissue and bone growth, and vascular malformations. Genital involvement is uncommon. We report a case of a 12-year-old female with KTS who experienced recurrent profuse vaginal bleeding and provide a comprehensive literature review on KTS cases with genital involvement. The literature reports 7 cases, mainly in individuals aged 25 to 45, presenting with uncontrollable vaginal bleeding and anemia. Endovascular interventions were the primary treatment, although surgery was necessary in some cases. Recent studies have identified a potential association between KTS and the PIK3CA gene mutation, offering insights for pharmacological treatment.

Examining the Influence of Warm-Up Static and Dynamic Stretching, as well as Post-Activation Potentiation Effects, on the Acute Enhancement of Gymnastic Performance: A Systematic Review with Meta-Analysis.

The primary objective of this systematic review with meta-analysis is to methodically discern and compare the impact of diverse warm-up strategies, including both static and dynamic stretching, as well as post-activation potentiation techniques, on the immediate performance of gymnasts. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this paper evaluated studies that examined the gymnasts' performance after different warm-up strategies namely stretching (static [SS] or dynamic), vibration platforms (VP) or post-activation, in comparison to control conditions (e.g., mixed warm-up routines; no warm-up). The principal outcomes were centered on technical performance metrics (e.g., split, gymnastic jumps) and physical performance metrics (e.g., squat jump, countermovement jump, drop jump, balance, range of motion). Methodological assessments of the included studies were conducted using the Downs and Black Checklist. From the initial search across PubMed, Scopus, and the Web of Science databases, a total of 591 titles were retrieved, and 19 articles were ultimately incorporated in the analysis. The results revealed a non-significant differences (p > 0.05) between the SS condition and control conditions in squat jump performance, countermovement jump and gymnastic technical performance (e.g., split; split jump). Despite the difference in warm-up strategies and outcomes analyzed, the results suggest that there is no significant impairment of lower-limb power after SS. Additionally, technical elements dependent on flexibility appear to be enhanced by SS. Conversely, dynamic stretching and VP seem to be more effective for augmenting power-related and dynamic performance in gymnasts.

Uniform Homeostatic Stress Through Individualized Interval Training Facilitates Homogeneous Adaptations Across Rowers With Different Profiles.

PURPOSE: This study compared the effects of individualizing supramaximal interval rowing interventions using anaerobic power reserve (APR [high-intensity interval training (HIIT) prescribed according to individual APR (HIITAPR)]) and power associated with maximal oxygen uptake (WV˙O2max [HIIT prescribed based on the individual WV˙O2max (HIITW)]) on the homogeneity of physiological and performance adaptations. METHODS: Twenty-four well-trained rowers (age 24.8 [4.3] y, stature 182.5 [3] cm, body mass 86.1 [4.3]) were randomized into interventions consisting of 4 × 30-second intervals at 130%APR (WV˙O2max + 0.3 × maximal sprint power) with weekly progression by increasing the number of repetitions per set (5, 6, 7, 8, 9, and 10, from first to sixth session) and the same sets and repetitions with the intensity described as 130% WV˙O2max. The work-to-recovery ratio was 1:1 for repetitions and 3 minutes between sets. Responses of aerobic fitness indices, power output, cardiac hemodynamics, locomotor abilities, and time-trial performance were examined. RESULTS: Both HIITAPR and HIITW interventions significantly improved V˙O2max, lactate threshold, cardiac hemodynamics, and 2000-m performance, with no between-groups difference in changes over time. However, HIITAPR resulted in a lower interindividual variability in adaptations in V˙O2max and related physiological parameters, but this is not the case for athletic performance, which can depend on a multitude of factors beyond physiological parameters. CONCLUSIONS: Results demonstrated that expressing supramaximal interval intensity as a proportion of APR facilitates imposing the same degrees of homeostatic stress and leads to more homogeneous physiological adaptations in maximal variables when compared to prescribing a supramaximal HIIT intervention using WV˙O2max. However, lower interindividual variability would be seen in submaximal variables if HIIT interventions were prescribed using WV˙O2max.

Effect of roasting and high-pressure homogenization on texture, rheology, and microstructure of walnut yogurt.

The effect of roasting and high-pressure homogenization on the quality of yogurt made from peeled walnut kernels was explored in this study. The G' and G'' values of yogurt made from walnuts roasted at high temperatures were reduced. The water-holding capacity and hardness of walnut yogurt were reduced to 47.73% and 24.22 g, respectively. Increasing the homogenization pressure reduced the particle size of the walnut yogurt to 20.50 µm. Homogenized walnut milk at 150 MPa increased the viscosity, hardness, and consistency of yogurt product from 11.71 to 16.74 Pa.s, from 30.01 to 71.63 g and from 283.17 to 455.24 g·s, respectively. The confocal laser scanning microscope observation demonstrated a reduction in the size of fat and protein micelles in the homogenized yogurt samples, resulting in a compact structure. This study will contribute valuable scientific insights to the advancement of plant-based yogurt quality.

Trocar puncture with modified sump drainage for duodenal stump fistula after radical gastrectomy for gastric cancer: A retrospective controlled study.

Duodenal stump fistula (DSF) is a serious complication of radical gastrectomy for gastric cancer. Herein, we illustrated an innovative choice for treating duodenal stump fistulas by placing a modified sump drainage through trocar puncture into the DSF-related abscess (DSF-abscess) cavity. We retrospectively analyzed 974 consecutive patients who underwent gastrectomy for gastric cancer between 2011 and 2021. Of these patients, 34 who developed postoperative duodenal stump fistulas postoperatively were enrolled into our study, and their clinical data were retrospectively assessed. From January 2011 to December 2017, 15 patients received conventional treatments (percutaneous catheter drainage, PCD group) known as the traditional percutaneous method, and 19 patients from January 2018 to December 2021 received new treatments (Troca's SD group) consisting of conventional therapies and placement of a modified sump drainage through trocar puncture into DSF-abscess cavity. The demographics, clinical characteristics and treatment outcomes were compared between two groups. Compared with the PCD group, the rates of postoperative complications, duodenostomy creation, subsequent surgery, fistula healing rates of the DSF, and length of postoperative hospital stay were significantly decreased in the Troca SD group. However, there was no significant difference in the abscess recurrence rate and mortality rates. Trocar puncture with a modified sump drainage is an safe, effective, and technically feasible treatment for duodenal stump fistula after radical gastrectomy for gastric cancer. This novel technique should be further investigated using large-scale RCT research.

Effects of plateau hypoxia on population pharmacokinetics and pharmacodynamics of metformin in patients with Type 2 diabetes. / 高原低氧对2åž‹ç³–å°¿ç— æ‚£è€ äºŒç”²åŒèƒç¾¤ä½“è¯åŠ¨å­¦å’Œè¯æ•ˆå­¦çš„å½±å“ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Metformin is the basic drug for treating diabetes, and the plateau hypoxic environment is an important factor affecting the pharmacokinetics of metformin, but there have been no reports of metformin pharmacokinetic parameters in patients with diabetes mellitus type 2 (T2DM) in the high-altitude hypoxic environment. This study aims to investigate the effect of the hypoxic environment on the pharmacokinetics and assess the efficacy and safety of metformin administration in patients with Type 2 diabetes mellitus (T2DM). METHODS: A total of 85 patients with T2DM taking metformin tablets in the plateau group (n=32, altitude: 1 500 m) and control group (n=53, altitude: 3 800 m) were enrolled according to the inclusion and exclusion criteria, and 172 blood samples were collected in the plateau group and the control Group. A ultra-performance liquid chromatography/tandem mass spectrometry (UFLC-MS/MS) method was established to determine the blood concentration of metformin, and Phoenix NLME software was used to establish a model of pharmacokinetics of metformin in the Chinese T2DM population. The efficacy and serious adverse effects of metformin were compared between the 2 groups. RESULTS: The population pharmacokinetic modeling results showed that plateau hypoxia and age were the main covariates for model building, and the pharmacokinetic parameters were significantly different between the plateau and control groups (all P<0.05), including distribution volume (V), clearance (CL), elimination rate constant (Ke), half-life(T1/2), area under the curve (AUC), time to reach maximum concentration (Tmax). Compared with the control group, AUC was increased by 23.5%, Tmax and T1/2 were prolonged by 35.8% and 11.7%, respectively, and CL was decreased by 31.9% in the plateau group. The pharmacodynamic results showed that the hypoglycaemic effect of T2DM patients in the plateau group was similar to that in the control group, the concentration of lactic acid was higher in the plateau group than that in the control group, and the risk of lactic acidosis was increased after taking metformin in the plateau population. CONCLUSIONS: Metformin metabolism is slowed down in T2DM patients in the hypoxic environment of the plateau; the glucose-lowering effect of the plateau is similar, and the attainment rate is low, the possibility of having serious adverse effects of lactic acidosis is higher in T2DM patients on the plateau than on the control one. It is probably suggested that patients with T2DM on the plateau can achieve glucose lowering effect by extending the interval between medication doses and enhancing medication education to improve patient compliance.

A study protocol for investigating the sonographic characteristics of neonates with critical illness: an observational cohort study.

BACKGROUND: Haemodynamic instability and hypoxaemia are common and serious threats to the survival of neonates. A growing body of literature indicates that critical care ultrasound has become the optimal evaluation tool for sick neonates. However, few studies have described sonographic characteristics of haemodynamics systematically in the neonates with critical illness. This protocol describes a prospective observational cohort study aimed at (1) characterising the sonographic characteristics of the neonates with critical diseases; and (2) assessing the mortality, significant morbidity, utility of vasoactive medications, fluid resuscitation, duration of ventilation, etc. METHODS AND ANALYSIS: This is a single-centre, prospective and observational study conducted in Chengdu Women's and Children's Central Hospital from 1 December 2022 to 31 December 2027. Neonates admitted to the neonatal intensive care unit will be recruited. After inclusion, the neonates will undergo the neonatal critical care ultrasound. The data collected via case report forms include clinical variables and sonographic measures. The primary outcome is to identify the sonographic characteristics of sick neonates with different diseases, and the secondary outcome is to describe the mortality, significant morbidity, utility of vasoactive medications, fluid resuscitation and duration of ventilation. DISCUSSION: Our study provided an organised neonatal critical care ultrasound workflow, which can be applied in practice. Accordingly, this study will first set up large data on the sonographic description of the neonates with critical illness, which can help to understand the pathophysiology of the critical illness, potentially titrating the treatment. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2200065581; https://www.chictr.org.cn/com/25/showproj.aspx?proj=184095).

Leaching of organic matters and formation of disinfection by-product as a result of presence of microplastics in natural freshwaters.

Microplastics (MPs) are ubiquitous in the environment that may cause negative impacts on the aquatic organisms and human health. They exist in water and wastewater, which are from several sources, such as inappropriate disposal and littering. Therefore, it is important to evaluate the characteristics of MPs in different water types and oxidation processes and study dissolved organic carbon (DOC) leaching and chloroform formation. A commonly existing plastic matter, polyethylene (PE) was placed in different waters and gone through the Fenton-like reaction and the chlorination. The result showed that the PE leached nearly a similar amount of DOC (<1 mg L-1), which was regardless of the water types and under low-dosed irradiation/dark environment. The leached DOC caused the chloroform formation after the chlorination in the waters. During the Fenton-like reaction with the PE, a higher amount of leached DOC (∼3 mg L-1) was detected compared with that in the chlorination (∼0.8 mg L-1). The degree of DOC leaching from the PE caused by the oxidation processes was reflected by the degree of surface structural damage on the PE. However, the chlorination resulted in a higher chloroform formation from the PE (∼20 µg L-1) as the Fenton-like reaction degraded the chloroform. The higher the sodium hypochlorite concentration, the higher the chloroform concentration. When the chloroform existed in the water with the PE, adsorption of chloroform onto the PE was initially observed; however the rate of volatilization would be higher than the rate of adsorption eventually. This study offers useful information for the risk assessment of MPs in our fresh water and drinking water and possible mitigation strategies.

LncRNA as a multifunctional regulator in cancer multi-drug resistance.

BACKGROUND: Malignant tumors have become the most dangerous disease in recent years. Chemotherapy is the most effective treatment for this disease; however, the problem of drug resistance has become even more common, which leads to the poor prognosis of patients suffering from cancers. Thus, necessary measures should be taken to address these problems at the earliest. Many studies have demonstrated that drug resistance is closely related to the abnormal expressions of long non-coding RNAs (lncRNAs). METHODS AND RESULTS: This review aimed to summarize the molecular mechanisms underlying the association of lncRNAs and the development of drug resistance and to find potential strategies for the clinical diagnosis and treatment of cancer drug resistance. Studies showed that lncRNAs can regulate the expression of genes through chromatin remodeling, transcriptional regulation, and post-transcriptional processing. Furthermore, lncRNAs have been reported to be closely related to the occurrence of malignant tumors. In summary, lncRNAs have gained attention in related fields during recent years. According to previous studies, lncRNAs have a vital role in several different types of cancers owing to their multiple mechanisms of action. Different mechanisms have different functions that could result in different consequences in the same disease. CONCLUSIONS: LncRNAs closely participated in cancer drug resistance by regulating miRNA, signaling pathways, proteins, cancer stem cells, pro- and ant-apoptosis, and autophagy. lncRNAs can be used as biomarkers of the possible treatment target in chemotherapy, which could provide solutions to the problem of drug resistance in chemotherapy in the future.

Regulatory Mechanisms of LncRNAs in Cancer Glycolysis: Facts and Perspectives.

Cancer cells exhibit distinct metabolic characteristics that employ glycolysis to provide energy and intermediary metabolites. This aberrant metabolic phenotype favors cancer progression. LncRNAs are transcripts longer than 200 nucleotides that do not encode proteins. LncRNAs contribute to cancer progression and therapeutic resistance and affect aerobic glycolysis via multiple mechanisms, including modulating glycolytic transporters and enzymes. Further, dysregulated signaling pathways are vital for glycolysis. In this review, we highlight regulatory mechanisms for lncRNAs in aerobic glycolysis that provide novel insights into cancer development. Moreover, a comprehensive understanding of the regulatory mechanisms of lncRNAs in aerobic glycolysis can provide new strategies for clinical cancer management.

Polysaccharides from Ganoderma Sinense - rice bran fermentation products and their anti-tumor activities on non-small-cell lung cancer.

BACKGROUND: Non-small-cell lung cancer (NSCLC) accounts more than 80% of the lung cancer cases. Polysaccharides in rice bran and its fermentation products have been proven to suppress many cancers. However, the report on inhibiting NSCLC is few. In this paper, the polysaccharides with suppression activity to H1299 NSCLC in the fermentation products of full-fat rice bran and defatted rice bran were studied in vitro and in vivo. METHOD: Polysaccharides (GSRBPs) were extracted from Ganoderma sinense - full-fat rice bran (GS-FRB) and Ganoderma sinense - defatted rice bran (GS-DRB) fermentation products. The structure information of the GSRBPs was studied using HPLC analysis. The anti-tumor activities on H1299 NSCLC of GSRBPs in vitro study was performed using MTT method. The in vivo studies use BALB/c-nu nude mice as H1299 NSCLC bearing mice. RESULT: All the polysaccharides contained two fractions, GSFPS-1 and GSFPS-2. The molecular weight and the ratio of GSFPS-1 and GSFPS-2 were different in GS-FRB and GS-DRB. At the earlier state of fermentation, all polysaccharides were composed of D-glu, D-man, D-xyl and L-ara with certain molar ratios. But at the latter stage, polysaccharides in GS-FRB were composed of D-glu, D-man, D-xyl, L-ara and D-fru, while these in GS-DRB only composed of D-glu and D-man. In the in vitro study, the IC50 of RBS and GSRBPs was as GS-DRB-11 (40.62 µg/mL), GS-FRB-9 (43.82 µg/mL), GS-DRB-7 (48.08 µg/mL), RBS (49.56 µg/mL), GS-DRB-9 (49.91 µg/mL), GS-DRB-13 (51.89 µg/mL), GS-FRB-11 (53.75 µg/mL), GS-FRB-7 (56.84 µg/mL), GS-DRB-13 (60.63 µg/mL) from small to large. In the in vivo study, the H1299 NSCLC inhibition rate (InRa) of RBS and GSRBPs were GS-DRB-11 (86.81%) > GS-DRB-9 (86.01%) > GS-FRB-9 (84.88%) > GS-DRB-7 (82.21%) > GS-DRB-13 (78.04%) > RBS (76.06%) > GS-FRB-13 (65.44%) > GS-FRB-11 (64.70%) > GS-FRB-7 (27.87%). The GSFPS-2 area percent was negatively correlated to the IC50 and was positively correlated to the InRa. This means the GSFPS-2 had much higher anti-tumor activity than GSFPS-1. CONCLUSION: GSFPS-2 had higher anti-tumor activities, and the lipid in the rice bran has a decisive effect on the structures of polysaccharides produced by fermentation. Therefore, GSRBPs could be considered as potential novel agents to suppress H1299 non-small-cell lung cancer.

PD-1/PD-L1 immune checkpoint blockade-based combinational treatment: Immunotherapeutic amplification strategies against colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant tumours of the digestive system, and most patients are already in an advanced stage at the time of diagnosis. Moreover, current single-use immune checkpoint inhibitors (ICIs), such as programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, are only effective for some advanced CRC patients with microsatellite instability-high (MSI-H), and most patients may be unable to benefit from it due to a lack of CD8+ T cells in the tumour microenvironment. Additionally, the subtype of CRC has emerged as a factor affecting treatment responses, with immunogenic subtypes carrying a better prognosis. In this review, we discuss bottlenecks encountered with the single use of PD-1/PD-L1 inhibitors and summarize the research status and mechanisms of PD-1/PD-L1 inhibitor-based immunotherapeutic amplification strategies, including chemotherapy, radiotherapy, photomediated therapy and other immunotherapies used for colorectal cancer.

Imperatorin alleviated endometriosis by inhibiting the activation of PI3K/Akt/NF-κB pathway in rats.

AIMS: Most therapeutic drugs of endometriosis have been contraceptives but symptoms recur in up to 75% of cases, which makes it a presses need to try to find novel and safer therapeutic drugs. Imperatorin is a furanocoumarin existing in many plants, possessing multiple activities, including anti-inflammatory. The purpose of this study was to assess the effects and mechanisms of imperatorin in endometriosis. MAIN METHODS: Ectopic endometrial volume and hematoxylin-eosin staining were used to estimate the effects of imperatorin in experimental endometriosis model rats. Potential mechanisms of imperatorin in endometriosis were systematically analyzed by network pharmacology and molecular docking. Western blotting and enzyme-linked immunosorbent assay were employed to evaluate proteins expression and cytokines levels in PI3K/Akt/NF-κB pathway. KEY FINDINGS: Imperatorin could significantly inhibit the growth and ameliorate the histopathological features of ectopic endometrium in experimental endometriosis rats. Network pharmacology approaches showed that imperatorin might regulate inflammatory response and cellular function via primarily affecting PI3K-Akt pathway, Endocrine resistance, Th17 cell differentiation in endometriosis. Moreover, 7 core targets (PIK3CA, AKT1, SRC, MAPK8, MAPK14, ERBB2 and CCND1) resulted from the intersection of KEGG and PPI network topological analysis were used to dock with imperatorin, which indicated that imperatorin could preferably fit in the binding pocket of the above target proteins, except for CCND1. Lastly, imperatorin markedly inhibited the activation of PI3K/Akt/NF-κB pathway via suppressing the phosphorylation levels of PI3K, Akt and p65 in the ectopic endometrium tissue. SIGNIFICANCE: Our findings revealed that imperatorin is a significant multi-target natural active ingredient for treatment endometriosis.

Icariin-induced inhibition of SIRT6/NF-κB triggers redox mediated apoptosis and enhances anti-tumor immunity in triple-negative breast cancer.

Abnormal activation of the nuclear factor-kappa B (NF-κB) signaling pathway is closely implicated in triple-negative breast cancer growth, metastasis, and tumor immune escape. In this study, the anti-cancer effects of icariin, a natural flavonol glycoside, toward breast cancer cells and the underlying mechanisms were investigated. This investigation showed that icariin selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration- and time-dependent manner, but exhibited little cytotoxicity in normal breast cells. Moreover, icariin induced cell apoptosis via a mitochondria-mediated pathway, as indicated by the upregulated ratio of Bax/Bcl-2 and reactive oxygen species induction. Importantly, icariin impaired the activation of the NF-κB/EMT pathway, as evidenced by upregulation of SIRT6, resulting in inhibition of migration and invasion of breast cancer cells. Additionally, oss-128167, an inhibitor of SIRT6, dramatically attenuated anti-migration and anti-invasion effects of icariin. Transcriptomic analysis verified that impairment of NF-κB led to the selective function of icariin in breast cancer cells. Notably, icariin exhibited a significant tumor growth inhibition and anti-pulmonary metastasis effect in a tumor mouse model of MDA-MB-231 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Together, these results showed that icariin could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the SIRT6/NF-κB signaling pathway, suggesting that icariin might serve as a potential candidate drug for the treatment of breast cancer.

Baicalin, a Potent Inhibitor of NF-κB Signaling Pathway, Enhances Chemosensitivity of Breast Cancer Cells to Docetaxel and Inhibits Tumor Growth and Metastasis Both In Vitro and In Vivo.

OBJECTIVE: The aim of this study is to investigate the anti-cancer activity and sensibilization of baicalin (BA) against breast cancer (BC) cells. METHODS: The anti-proliferation of BA in BC cell lines was evaluated by MTT and colony formation assays. Apoptotic induction of BA was measured by flow cytometry. Wound-healing and transwell assays were exploited to assess migrated and invasive inhibition of BA. Western-blot and immunofluorescence were used to study mechanisms of anti-migration and sensibilization of BA. Anti-tumor and anti-metastasis effects of BA were evaluated in subcutaneous and pulmonary metastasis mouse model of BC cells. RESULTS: BA significantly suppressed proliferation and induced apoptosis of BC cells in a concentration- and time-dependent manner. Additionally, BA induced cell apoptosis via the mitochondria-mediated pathway, as evidenced by cellular induction of reactive oxygen species and upregulated expression of the Bax/Bcl-2 ratio. The overall expression and nuclear translocation of NF-κB signaling pathway in BC cells were dramatically inhibited by treatment with BA. BA significantly suppressed abilities of migration and invasion in BC cells. Notably, BA sensitized BC cells to docetaxel (DXL) by suppressing the expression of survivin/Bcl-2. BA also retarded tumor growth and triggered apoptosis of tumor cells in a tumor mouse model of 4T1 cells. Furthermore, pulmonary metastasis of BC cells was distinctly suppressed by BA in a tumor mouse model of 4T1 cells. CONCLUSION: BA effectively triggered apoptosis, inhibited metastasis, and enhanced chemosensitivity of BC, implying that BA might serve as a promising agent for the treatment of BC.

Extensive serum biomarker analysis in patients with non-small-cell lung carcinoma.

Lung cancer is a common malignant disease, nearly 2.09 million new patients occurred last year. Approximately 85% of the patients are classified as non-small-cell lung cancer (NSCLC). It is therefore important to identify new diagnostic and prognostic biomarkers for the early detection of this disease. The presented study identifies biomarkers in the serum of NSCLC patients. The expression of 274 cytokines was measured by a novel antibody array methodology and ELISA was applied to validate the array results. The levels of MIP-1 α, IL-8, MIP-1 ß, Resistin, GDF-15, HGF, CA125, FLRG, VCAM-1, DKK-3, sTNF-R1, CTACK, Acrp30, CXCL-16 and LYVE-1 were significantly higher in serum from NSCLC patients, while the level of TIMP-2 and IGFBP-6 were lower. More importantly, the validation supported the result of the antibody array. The result of the antibody array indicates that these cytokines might be novel auxiliary biomarkers in the diagnosis and prognosis of NSCLC.

Effectiveness of methotrexate in combination therapy in a rat collagen-induced arthritis model.

This study was to investigate the effect of methotrexate in combination therapy by the characteristic cytokine in Th17 cells and the frequency of Tregs, which involved in the induction and pathological progress of rheumatoid arthritis (RA). The collagen-induced arthritis rats were treated with methotrexate + prednisone, methotrexate + disease-modifying rheumatic drugs (DMARDs) and methotrexate + TNFi, respectively. The following parameters were observed to evaluate three treatments: the frequency and function of Th17 cells and Tregs, the scores of X-rays, H&E staining and immunohistochemistry. For rats starting methotrexate + prednisone (low doses), the frequency and suppressive function of Th17 cells decreased while the frequency of Tregs increased, which were the same in methotrexate + TNFi. Immunohistochemical in the pathological sections of ankle joint showed the same results. The effect of methotrexate + DMARDs treatment was slightly inferior to the other combination therapies. In summary, rats treated with methotrexate + prednisone can achieve high level of Tregs and low level of Th17 cells and IL-17. Low doses of glucocorticoid suggesting a critical role in the pathogenesis of rheumatoid arthritis may have the similar effect as DMARDs.