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Background: Most materials used clinically for filling severe bone defects either cannot induce bone re-generation or exhibit low bone conversion, therefore, their therapeutic effects are limited. Human umbilical cord mesenchymal stem cells (hUC-MSCs) exhibit good osteoinduction. However, the mechanism by which combining a heterogeneous bone collagen matrix with hUC-MSCs to repair the bone defects of alveolar process clefts remains unclear.Methods: A rabbit alveolar process cleft model was established by removing the bone tissue from the left maxillary bone. 48 young Japanese white rabbits (JWRs) were divided into normal, control, material and MSCs groups. An equal volume of a bone collagen matrix alone or combined with hUC-MSCs was implanted in the defect. X-ray, micro-focus computed tomography (micro-CT), blood analysis, histochemical staining and TUNEL were used to detect the newly formed bone in the defect area at 3 and 6 months after the surgery. Results: The bone formation rate obtained from the skull tissue in MSCs group was significantly higher than that in control group at 3 months (PPPPConclusions: Combining bone collagen matrix with hUC-MSCs promoted the new bone regeneration in the rabbit alveolar process cleft model through promoting osteoblasts formations and chondrocyte growth, and inducing type 1 collagen formation and BMP-2 generation.

Objective: A model of alveolar cleft phenotype was established in rabbits to evaluate the effect of active bone particles containing modified rhecombinant human BMP-2 on the repair of the alveolar cleft. Methods: 2-month-old Japanese white rabbits were selected and randomly divided into four groups: normal, control, material and BMP groups. Blood biochemical analysis, skull tomography (microfocus computerized tomography), and histological and immunohistochemical staining analysis of paraffin sections were performed 3 and 6 months after operation. Results: Both types of collagen particles showed good biocompatibility and promoted bone regeneration. The effect of active bone particles on bone repair and regeneration was better than that of bone collagen particles. Conclusions: Active bone particles containing modified rhecombinant human BMP-2 can be used for incisors regeneration.

Recent clinical trials of lung adenocarcinoma with immune checkpoint inhibitors revealed that lung adenocarcinoma patients with EGFR mutations have a poor response to immunotherapy. However, the mechanisms have not been addressed. We performed immunohistochemistry analyses of resected lung adenocarcinoma tissues with and without EGFR mutations to investigate and compare the characteristics of the tumor microenvironment (TME). We retrospectively enrolled a total of 323 lung adenocarcinoma patients (164 had EGFR mutations), and their corresponding tissue samples were analyzed by the EGFR mutation test and immunohistochemistry. We selected the markers of the immune checkpoint molecule (PD1, PD-L1, and LAG-3) and immune cell (CD3, CD4, CD8, and Foxp3) as markers of the tumor microenvironment. Our results revealed that patients had a distinct tumor microenvironment between EGFR-mutant and wild-type lung adenocarcinomas; the expression of CD3, CD4, PD-L1, and Foxp3 in EGFR-mutant tumors was significantly higher than that in wild-type tumors, while the expression of LAG3 and PD-1 showed a positive correlation with EGFR-wild-type tumors. In survival analysis, EGFR-wild-type patients had longer disease-free survival (DFS) than EGFR-mutant patients ( P = 0.0065 ). Our research demonstrates significant differences in tumor microenvironment composition between EGFR-mutant and wild-type patients. Our findings provide novel evidence that contributes to understanding the mechanism underlying the poor efficacy of immune checkpoint inhibitors.

Background The clinical application of most materials used to fill severe bone defects is limited owing to the insufficient ability of such materials to induce bone regeneration or the long repair period. The purpose of this study was to establish a model for the alveolar process cleft in rabbits to evaluate the effect of active bone material in bone defect repair. The active bone material used in this study is a new bone repair material composed of a heterogeneous collagen membrane implanted with modified recombinant human bone morphogenetic protein 2 (rhBMP-2). This proposed active bone material can specifically bind to collagen. Methods Twenty-four young Japanese white rabbits (JWRs) were selected and randomly divided into four groups (normal, control, material and BMP groups). The alveolar process cleft model was established by removing an equal-volume bone at the left maxillary position. Blood samples were collected from the JWRs 3 and 6 months after the surgery to evaluate the biocompatibility of the active bone materials. Subsequently, the skull model was established, and the appearance was observed. Imaging methods (including X-ray examination and Micro-computerized tomography (CT) scanning), tissue engineering staining and immunohistochemistry were employed for the evaluation. Results The bone collagen material and active bone material exhibited high biocompatibility. In addition, the ability of the active bone material to induce bone repair and regeneration was higher than that of the bone collagen material. Conclusions The active bone material exhibited satisfactory bone regeneration performance in rabbits, indicating its potential as an active material for repairing congenital alveolar process clefts in humans.

Background Alveolar cleft is a type of cleft lip and palate that seriously affects the physical and mental health of patients. In this study, a model of the alveolar cleft phenotype was established in rabbits to evaluate the effect of bone collagen particles combined with human umbilical cord mesenchymal stem cells (HUC-MSCs) on the repair of alveolar cleft bone defects. Methods A model of alveolar clefts in rabbits was established by removing the incisors on the left side of the upper jaw bone collagen particles combined with HUC-MSCs that were then implanted in the defect area. Blood biochemical analysis was performed 3 months after surgery. Skull tissues were harvested for gross observation, and micro-focus computerised tomography (micro-CT) analysis. Tissues were harvested for histological and immunohistochemical staining. The experiments were repeated 6 months after surgery. Results Bone collagen particles and HUC-MSCs showed good biocompatibility. Bone collagen particles combined with HUC-MSCs were markedly better at inducing bone repair and regeneration than bone collagen particles alone. Conclusions Combining HUC-MSCs with bone collagen particles provides a simple, rapid and suitable method to fill a bone defect site and treat of alveolar cleft bone defects.

Background: Alveolar cleft is a kind of cleft lip and palate, which seriously affects the physical and mental health of patients. In this study, a similar model of human alveolar cleft phenotype was established in rabbits to evaluate the effect of bone collagen particles combined with human umbilical cord mesenchymal stem cells (hUC-MSCs) on the repair of alveolar cleft bone defects. Methods: In this study, 24 adult Japanese white rabbits (JWRs) were selected and randomly divided into 4 groups. Including normal group, control group, materials group and MSCs group. The model of alveolar clefts was established by removing the incisors on the left side of the upper jaw. The normal group did nothing. In the control group, the incisors were removed and sutured directly. In the material group, the incisor were removed, then filled with bone collagen particles, and finally sutured. In the MSCs group, the incisors were first removed, then filled with bone collagen particles incubated by hUC-MSCs, and then stitched. Blood biochemical analysis was performed 3 months after the operation. Skull tissues were collected for gross observation, and micro-focus computerized tomography (micro-CT) analysis. Paraffin sections were prepared for histological and immunohistochemical staining. Results: The bone collagen particles and hUC-MSCs are not biotoxic and can promote alvenlus regeneration. Bone collagen particles combined with hUC-MSCs were much better than those used alone in inducing bone repair and regeneration. Conclusions: HUC-MSCs can be used as a bone generation inducer combined with bone collagen materials for bone regeneration and repair.

Objective Cleft palate is one of the most common craniofacial birth defects in the maxillofacial region. There is an urgent need in tissue regeneration research to establish animal models that faithfully mimic human diseases. Here, we compared three surgical models of bone tissue defects in cleft palate in rabbits in order to screen for the biomaterials that induced optimal bone regeneration. Design Rabbits were used to establish the models of hard palate cleft, alveolar cleft, and alveolar process cleft. Eight weeks following surgery, bone tissue self-healing capacity was estimated by macroscopic appearance and calculating the area of defective bone tissue. The dimensions of the upper jaw in left and right sides were measured at zero and eight weeks. Results Bone defects in three types of cleft palate models were made at the positions of the hard palate, alveoli and alveolar process. After 8 weeks, when the hard palate was partially excised, it underwent self-healing. When the hard palate was completely excised, it underwent partial self-healing. However, in the models of alveolar cleft and alveolar process cleft, there was no significant self-healing in the bone tissues. The dimensions of the upper jaw in left and right sides were no significant differences in three types of cleft palate models. Conclusions Bone defects in the alveolar and alveolar process clefts exhibit a diminished capability for self-healing. This study may provide valuable information for the screening of materials that induce bone regeneration.

Herein we report a new separable detection system combining magnetic nanoparticle labels with giant magnetoresistance (GMR) first time developed for Escherichia coli (E. coli) O157H:H7 detection. The GMR sensor fabricated employing standard microfabrication technique, while double antibody sandwich immunoassay and streptavidin–biotin binding assay were employed for immobilizing and labeling E. coli O157H:H7 on Au-film coated glass wafer. The GMR-based immunosensor detected E. coli O157H:H7 antigens at different sample concentrations with a minimum detectable limit of 100 CFU/mL, well accepted for early detection in clinical diagnosis and environmental monitoring. Compared with the recently reported GMR sensor based detection methods, this newly developed separable detection method possesses several advantages such as convenient manipulation, avoid being contaminated and damaged by chemical solution and reusability without cleaning. So it is of considerable interest towards the biomedical application based on known specific binding of target and labels.

BACKGROUND Inflammation is considered as one of the main pathogeneses in OA-induced pain. Macrophage migration inhibitory factor (MIF) is a well known pro-inflammatory cytokine. We aimed to determine whether MIF levels in serum and synovial fluid (SF) are associated with severity of OA-induced pain. MATERIAL AND METHODS We recruited 226 patients with knee OA and 106 controls. Self-reported pain severity of OA patients was evaluated using the Western Ontario McMaster University Osteoarthritis (WOMAC) pain scores. MIF levels were detected using enzyme-linked immunosorbent assay (ELISA). RESULTS OA patients had similar serum MIF levels compared to controls (11.93 [5.68-18.10] vs. 10.06 [6.60-14.61] ng/ml, P>0.05). In OA patients, MIF levels in SF were dramatically lower compared to paired serum samples (3.39 [1.87-5.89] vs. 11.93 [5.68-18.10] ng/ml, P

We report on a method for ultrasensitive detection and quantification of the pathogen Escherichia coli (E. coli), type O157:H7. It is using a tortuous-shaped giant magnetoimpedance (GMI) sensor in combination with an open-surface microfluidic system coated with a gold film for performing the sandwich immunobinding on its surface. Streptavidin-coated super magnetic Dynabeads were loaded with biotinylated polyclonal antibody to capture E. coli O157:H7. The E. coli-loaded Dynabeads are then injected into the microfluidics system where it comes into contact with the surface of gold nanofilm carrying the monoclonal antibody to form the immunocomplex. As a result, the GMI ratio is strongly reduced at high frequencies if E. coli O157:H7 is present. The sensor has a linear response in the 50 to 500 cfu·mL−1 concentration range, and the detection limit is 50 cfu·mL−1 at a working frequency of 2.2 MHz. In our perception, this method provides a valuable tool for developing GMI-based microfluidic sensors systems for ultrasensitive and quantitative analysis of pathogenic bacteria. The method may also be extended to other sensing applications by employing respective immunoreagents.

We report on a giant magnetoresistance (GMR) based immunosensor for the carcinoembryonic antigen (CEA) labeled with superparamagnetic microparticles (Dynabeads). The GMR sensor contains 200 GMR strips and was fabricated by micro-electromechanical system (MEMS) technology. This system can detect Dynabeads in concentrations down to 10 ng⋅mL−1. Sandwich immunoassays were employed on the surface of a gold film modified with a self-assembled monolayer and using biotinylated secondary antibody against CEA and streptavidinylated Dynabeads. With DC magnetic fields in the range of 40 to 90 Oe, CEA can be detected with a detection limit as low as 10 pg⋅mL−1. Samples spiked with different concentrations of CEA can be distinguished clearly, and the method is deemed to be well suited for clinical use.

BACKGROUND/AIMS To investigate the efficacy and safety of endoscopic biliary stenting for difficult common bile duct (CBD) stones in elderly patients. MATERIALS AND METHODS Elderly patients (≥65 years) with large (≥20 mm) or multiple (≥3) CBD stones were studied. The patients underwent placement of single (n=34, group A) or double (n=30, group B) plastic stents at the time of initial endoscopic retrograde cholangiopancreatography (ERCP). Approximately 3 months later, stone removal was attempted at the second ERCP. The reduction of stone size and number before and after biliary stenting, complete stone removal, 3-month stent patency rate, and complications were compared. RESULTS The mean size (longitudinal/transverse diameter) of the CBD stones was significantly reduced after biliary stenting in both groups (p

We report an innovative integrated microfluidic platform based on micro-fluxgate and micro-coils for trapping and detecting magnetic beads. A micro-spiral coil fabricated by microfabrication technology is used to trap the magnetic beads, and the micro-fluxgate is employed to detect the weak magnetic field induced by the trapped magnetic beads. The fabrication process of the magnetic bead trapping system using a micro-coil is highly compatible with that of the micro-fluxgate sensor, making fabrication of this integrated microfluidic system convenient and efficient. It is observed that the magnetic bead trapping ratio increases as the number of magnetic beads is increased with a flow rate of 5 to 16.5 μL·min

Background/Aims: A growing body of evidence has suggested that thiazolidinediones (TZDs) potentially reduce the risk of colorectal cancer (CRC). This study aimed to evaluate the effect of TZDs on CRC risk in patients with diabetes mellitus (DM). Patients and Methods: A systematic search of electronic databases was performed for studies evaluating the exposure to TZDs and reporting CRC risk in diabetic patients. Pooled estimates with 95% confidence intervals (CIs) were estimated using fixed or random effects models. Results: A total of 10 observational studies reporting more than 18,972 CRC cases in 2,470,768 DM patients were included. Meta-analysis showed a 9% reduction in CRC risk associated with TZDs use in all studies [relative risk (RR) =0.91, 95% CI = 0.84–0.99, P = 0.03] and cohort studies (RR = 0.89, 95% CI = 0.80–0.99, P = 0.04), respectively. However, such effect was not shown in case–control studies. In subgroup analyses, lower CRC risk was found in Asian population (RR = 0.40, 95% CI = 0.29–0.53, P = 0.00), and a trend toward lower CRC risk was observed in US population (RR = 0.94, 95% CI = 0.88–1.01, P = 0.08). CRC risk was significantly modified with non-pioglitazone TZD use (RR = 0.88, 95% CI = 0.82–0.95, P = 0.00), but not with pioglitazone use (RR = 0.95, 95% CI = 0.89–1.01, P = 0.11). No significant difference was observed with cancer site (colon or rectum). There was considerable inherent heterogeneity across studies, partly explained by study location. Conclusions: This meta-analysis supports a protective association between TZDs use and CRC risk in patients with DM. Future well-designed prospective studies with larger cohorts would be needed to understand this association better.

A novel bio-sensing system based on a micro-fluxgate and use of magnetic beads labels was developed for detection of Escherichia coli O157H:H7. The micro fluxgate sensor was fabricated using standard microfabrication processes. Magnetic core of the sensor was made using Fe-based amorphous ribbon core and a 3-D magnetic sensitive element was made of Cu solenoid coils. Response of the micro-fluxgate-based bio-sensing system to superparamagnetic Dynabead was first evaluated with different concentrations of Dynabeads. It was found that a concentration as low as 10 ng/ml could be detected with an external dc magnetic field ranging from 450 μT to 700 μT. Double antibody sandwich assay was employed in preparation of E. coli O157H:H7 samples. Detection of E. coli O157H:H7 antigens at different concentrations were demonstrated. A minimum detectable concentration of 100 CFU/ml was observed for this bio-sensing system. On account of the detection performance and other advantages such as miniaturization, portability and stability, this bio-sensing system is a potential candidate for rapid analysis E. coli O157:H7 and other pathogenic bacteria. It is also of considerable interest for biomedical applications employing known specific binding of target and labels.

To investigate the efficiency and safety profile of the addition of S-1 to gemcitabine (GEM)-based chemotherapy for advanced pancreatic cancer (APC).Computerized search was undertaken to identify randomized controlled trials of S-1 plus GEM versus GEM monotherapy in APC patients. The outcomes included overall survival (OS), progression-free survival (PFS), response rate, and toxicities.Five studies with 917 patients were included. Overall, there was a significant difference between the two regimens in terms of OS (HR=0.83, 95%CI=0.72-0.96, P=0.01), PFS (HR=0.64, 95%CI=0.56-0.74, P0.0001), and overall response rate (ORR; RR=2.36, 95%CI=1.73-3.22, P0.00001). Occurrence of grade 3/4 hematological toxicities (neutropenia, thrombocytopenia) and non-hematological toxicities (diarrhea, nausea/vomit, rush, stomatitis/mucositis) were significantly higher with GEM/S-1 treatment.This meta-analysis indicated a significant survival benefit with increased toxicity when S-1 was combined with GEM. GEM/S-1 might be an option of first-line chemotherapy for APC patients, at least in Asia.

Magnetic bead-based biosensors are becoming a hot spot in biomedical fields. A Dynabeads-labeled immunoassay has been developed using a micro fluxgate biosensor for the detection of alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA). The micro fluxgate sensors with a rectangular permalloy core with sides of equal width and three-dimensional solenoid coils are fabricated by micro-electro-mechanical-system (MEMS) technology, including thick photoresist lithography and electroplating. The immune reaction of biomarkers is accomplished on a separated Au film substrate surface with a self-assembled layer. Sandwich immunoassay is used to specifically capture and label the biomarker. Dynabeads are conjugated into the biomarker by a streptavidin–biotin system. The micro fluxgate-based sensing system was characterized firstly in different concentrations of Dynabeads. It is found that a concentration as low as 0.1 μg ml−1 (90 Dynabeads) can be detected by this sensing system with an external magnetic field in the range of 643 μT to 1180 μT. The AFP and CEA with different concentrations were detected by the sensing system. The results reveal that a minimum detectable concentration of 1 pg ml−1 was achieved in the measuring ranges of 724 μT to 1150 μT for AFP, and 670 μT to 1110 μT for CEA. Compared with a micro fluxgate sensor with a ribbon core for the detection of biomarkers, the micro fluxgate sensor with an electroplated permalloy core possesses a wider linear measuring range, and could make it possible to integrate a micro fluxgate-based biosensing system produced on a large scale, with an expanded application field and reduced costs.

This paper presents a contactless detection method for detecting prostate specific antigen with a giant magnetoresistance sensor. In contactless detection case, the prostate specific antigen sample preparation was separated from the sensor that prevented the sensor from being immersed in chemical solvents, and made the sensor implementing in immediately reuse without wash. Experimental results showed that applied an external magnetic field in a range of 50 Oe to 90 Oe, Dynabeads with a concentration as low as 0.1 μg/mL can be detected by this system and could give an approximate quantitation to the logarithmic of Dynabeads concentration. Sandwich immunoassay was employed for preparing PSA samples. The PSA capture was implemented on a gold film modified with a self-assembled monolayer and using biotinylated secondary antibody against PSA and streptavidinylated Dynabeads. With DC magnetic field in the range of 50 to 90 Oe, PSA can be detected with a detection limit as low as 0.1 ng/mL. Samples spiked with different concentrations of PSA can be distinguished clearly. Due to the contactless detection method, the detection system exhibited advantages such as convenient manipulation, reusable, inexpensive, small weight. So, this detection method was a promising candidate in biomarker detection, especially in point of care detection.

A giant magnetoimpedance (GMI)-based biosensor was developed for detection of Escherichia coli (E. coli) O157: H7. The GMI sensor involving the sensing elements of Cr/Cu/NiFe/Cu/NiFe was fabricated by Micro Electro-Mechanical system (MEMS) technology, including thick photoresist lithography and electroplating. A separate Au film substrate as immunoplatform was used to capture E. coli O157:H7. The monoclonal mouse anti-E. coli antibody was immobilized on Au film substrate surface with a self-assembled layer. The different concentration E. coli O157:H7 (100, 300 and 500 cfu/ml) were combined with Dynabeads-antibody conjugates (DAC) respectively. DAC were prepared by conjugating streptavidin-coupled Dynabeads with biotin-labeled polyclonal mouse anti-E. coli antibodies. The classical sandwich assay was used for detection of E. coli O157:H7 targeted with Dynabeads by using antibody-antigen pair combination of biotin-streptavidin. The fundamental principle for detection of E. coli O157:H7 based on GMI sensor was that Dynabeads were employed as magnetic labels of E. coli O157:H7, and E. coli O157:H7 can be monitored by detecting the fringe field of Dynabeads using magnetic sensing elements. We observed that the GMI ratio were significantly improved due to the presence of E. coli O157:H7 combined with Dynabeads. The GMI ratio increased as the E. coli O157:H7 concentration increased. A lower detectable concentration of 100 cfu/ml was achieved in present work. The GMI-based biosensor provides a new method to rapid and sensitive detection E. coli O157:H7, which has a large potential for bio-application.

AIM: To assess the association between smoking and alcohol consumption and extrahepatic cholangiocarcinoma (ECC) through a meta-analysis of clinical observational studies. METHODS: A literature search was conducted using Embase and MEDLINE databases from inception to 31 May 2013 without language limitations, and by manually searching the references of retrieved articles. Case-control and cohort studies that investigated the association between smoking or alcohol consumption and ECC were included. The quality of these studies was assessed using the Newcastle-Ottawa quality assessment scale. Summary relative risks and corresponding 95%CI were calculated using a random-effects model. Publication bias was assessed by Begg’s funnel plot and Egger’s test. RESULTS: A total of 12 eligible articles (11 case-control studies and one cohort study) were included in this meta-analysis. Eleven studies reported the association between smoking and ECC. Pooled analysis indicated that smokers had an increased risk of ECC development as compared with non-smokers (summary RR = 1.23; 95%CI: 1.01-1.50). This correlation was present in population-based studies (n = 5; summary RR = 1.47; 95%CI: 1.06-2.05) but not in hospital-based studies (n = 6; summary RR = 1.10; 95%CI: 0.88-1.37) and in non-Asian regions (n = 7; summary RR = 1.39; 95%CI: 1.03-1.87) but not in Asia (n = 4; summary RR = 1.08; 95%CI: 0.85-1.38). Seven studies reported an association between consuming alcohol and ECC. Pooled analysis indicated that alcohol drinkers had a similar risk of ECC development as did individuals who did not drink alcohol (summary RR = 1.09; 95%CI: 0.87-1.37). There was moderate heterogeneity among the studies and no evidence of publication bias. CONCLUSION: Smoking is associated with an increased risk of ECC, but alcohol consumption is not. Further population-based studies, particularly cohort studies, are warranted to enable definitive conclusions.

Summary Aims To evaluate the efficiency and safety profile of raltitrexed-based chemotherapy in the treatment of advanced colorectal cancer. Methods An electronic search was undertaken to identify randomized controlled trials comparing raltitrexed-based regimen to 5-fluorouracil-based regimen in patients with advanced colorectal cancer. The outcomes included overall survival, overall response rate and toxicities. Results This meta-analysis included 11 studies with 4622 patients. Overall, there were no significant differences between the two regimens in terms of overall survival (HR = 1.06, 95% CI: 0.96–1.17, P = 0.23) or overall response rate (RR = 1.09, 95% CI: 0.86–1.38, P = 0.47). In subgroup analysis, patients in raltitrexed/oxaliplatin group had significantly higher partial response (RR = 1.53, 95% CI: 1.17–2.00, P = 0.002), overall response rate (RR = 1.42, 95% CI: 1.10–1.82, P = 0.006), disease control rate (RR = 1.16, 95% CI: 1.04–1.29, P = 0.009) and lower progressive disease (RR = 0.61, 95% CI: 0.45–0.84, P = 0.002) when compared to 5-fluorouracil/leucovorin/oxaliplatin group. Occurrence of severe anemia (RR = 2.23, 95% CI: 1.38–3.59, P = 0.0001), asthenia (RR = 2.29, 95% CI: 1.36–3.84, P = 0.002), hepatic disorders (RR = 7.51, 95% CI: 1.30–43.56, P = 0.02), and nausea/vomit (RR = 1.70, 95% CI: 1.03–2.81, P = 0.04) were significantly higher with the raltitrexed arm treatment, while frequencies of grade 3/4 alopecia (RR = 0.36, 95% CI: 0.26–0.50, P P Conclusions Raltitrexed-based chemotherapy regimen leads to an equivalent overall survival and response rates with acceptable toxicities compared to traditional 5-fluorouracil-based regimen in patients with advanced colorectal cancer. Raltitrexed can be a treatment option for these patients when 5-fluorouracil-based regimens are not tolerated or inappropriate.

To explore effects of telomerase RNA-targeting phosphorothioate antisense oligodeoxynucleotides (PS-ASODN) on growth of human gastrointestinal stromal tumors transplanted in mice.A SCID mouse model for transplantation of human gastrointestinal stromal tumors (GISTs) was established using tumor cells from a patient who was diagnosed with GIST and consequently had been treated with imatinib. GIST cells cultured for 10 passages were used for inoculation into mice. Transfection of PS-ASODN was carried out with Lipotap Liposomal Transfection Reagent. GISTs that subsequently developed in SCID mice were subjected to intra-tumoral injection once daily from day 7 to day 28 post-inoculation, and mice were divided into the following four groups according to treatment: PS-ASODN group (5.00 μmoL/L of oligonucleotide, each mouse received 0.2 mL once daily); imatinib group (0.1 mg/g body weight); liposome negative control group (0.01 mL/g); and saline group (0.01 mL/g). On day 28, the mice were sacrificed, and tumor attributes including weight and longest and shortest diameters were measured. Tumor growth was compared between treatment groups, and telomerase activity was measured by enzyme-linked immunosorbent assay. Apoptosis was examined by flow cytometry. Real-time polymerase chain reaction was used to detect expression of the mRNA encoding the apoptosis inhibition B-cell leukemia/lymphoma 2 (bcl-2) gene.In the PS-ASODN group, tumor growth was inhibited by 59.437%, which was markedly higher than in the imatinib group (11.071%) and liposome negative control group (2.759%) [tumor inhibition = (mean tumor weight of control group--mean tumor weight of treatment group)/(mean tumor weight of control group) × 100%]. Telomerase activity was significantly lower (P0.01) in the PS-ASODN group (0.689 ± 0.158) compared with the imatinib group (1.838 ± 0.241), liposome negative control group (2.013 ± 0.273), and saline group (2.004 ± 0.163). Flow cytometry revealed that the apoptosis rate of tumor cells treated with PS-ASODN was 20.751% ± 0.789%, which was higher (P0.01) than that of the imatinib group (1.163% ± 0.469%), liposome negative control group (1.212% ± 0.310%), and saline group (1.172% ± 0.403%). Expression of bcl-2 mRNA in the transplanted GISTs was markedly downregulated (P0.01) in the PS-ASODN group (7.245 ± 0.739) compared with the imatinib group (14.153 ± 1.618) and liposome negative control group (16.396 ± 1.351).PS-ASODN can repress GIST growth, mediated perhaps by inhibition of telomerase activity and downregulation of bcl-2 expression.

Objective Inflammation is implicated to be involved in the pathogenesis of osteoarthritis (OA). CXCL12, also known as stromal cell-derived factor, is the unique identified natural ligand of the G-protein-coupled receptor CXCR4 and exhibits both homeostatic and proinflammatory functions. This study aims to determine whether CXCL12 levels in serum and synovial fluid (SF) of patients with knee OA are correlated with the disease severity. Methods This study consisted of 252 patients with knee OA and 144 healthy controls. The radiological grading of OA in the knee was performed according to the Kellgren-Lawrence grading system. CXCL12 levels in serum and SF were measured by enzyme-linked immunosorbent assay. Results Higher levels of serum CXCL12 were found in knee OA patients compared with healthy controls. The CXCL12 levels in SF of knee OA patients with KL grade 4 were significantly elevated compared with those with KL grades 2 and 3. Furthermore, knee OA patients with KL grade 3 had significantly higher SF levels of CXCL12 compared with those with KL grade 2. CXCL12 levels in SF of knee OA patients were significantly correlated with disease severity evaluated by KL grading criteria. However, there were no significant differences in the serum CXCL12 levels between patients with different KL grades. Conclusion CXCL12 levels in SF were closely related to the radiographic severity of OA. CXCL12 levels in SF may be an alternative biomarker for the progression of OA.

To investigate whether therapeutic treatment with melatonin could protect rats against acute pancreatitis and its associated lung injury.Seventy-two male Sprague-Dawley rats were randomly divided into three groups: the sham operation (SO), severe acute pancreatitis (SAP), and melatonin treatment (MT) groups. Acute pancreatitis was induced by infusion of 1 mL/kg of sodium taurocholate (4% solution) into the biliopancreatic duct. Melatonin (50 mg/kg) was administered 30 min before pancreatitis was induced, and the severity of pancreatic and pulmonary injuries was evaluated 1, 4 and 8 h after induction. Serum samples were collected to measure amylase activities, and lung tissues were removed to measure levels of mRNAs encoding interleukin 22 (IL-22) and T helper cell 22 (Th22), as well as levels of IL-22.At each time point, levels of mRNAs encoding IL-22 and Th22 were significantly higher (P0.001) in the MT group than in the SAP group (0.526 ± 0.143 vs 0.156 ± 0.027, respectively, here and throughout, after 1 h; 0.489 ± 0.150 vs 0.113 ± 0.014 after 4 h; 0.524 ± 0.168 vs 0.069 ± 0.013 after 8 h, 0.378 ± 0.134 vs 0.122 ± 0.015 after 1 h; 0.205 ± 0.041 vs 0.076 ± 0.019 after 4 h; 0.302 ± 0.108 vs 0.045 ± 0.013 after 8 h, respectively) and significantly lower (P0.001) in the SAP group than in the SO group (0.156 ± 0.027 vs 1.000 ± 0.010 after 1 h; 0.113 ± 0.014 vs 1.041 ± 0.235 after 4 h; 0.069 ± 0.013 vs 1.110 ± 0.213 after 8 h, 0.122 ± 0.015 vs 1.000 ± 0.188 after 1 h; 0.076 ± 0.019 vs 0.899 ± 0.125 after 4 h; 0.045 ± 0.013 vs 0.991 ± 0.222 after 8 h, respectively). The mean pathological scores for pancreatic tissues in the MT group were significantly higher (P0.01) than those for samples in the SO group (1.088 ± 0.187 vs 0.488 ± 0.183 after 1 h; 2.450 ± 0.212 vs 0.469 ± 0.242 after 4 h; 4.994 ± 0.184 vs 0.513 ± 0.210 after 8 h), but were significantly lower (P0.01) than those for samples in the SAP group at each time point (1.088 ± 0.187 vs 1.969 ± 0.290 after 1 h; 2.450 ± 0.212 vs 3.344 ± 0.386 after 4 h; 4.994 ± 0.184 vs 6.981 ± 0.301 after 8 h). The severity of SAP increased significantly (P0.01) over time in the SAP group (1.088 ± 0.187 vs 2.450 ± 0.212 between 1 h and 4 h after inducing pancreatitis; and 2.450 ± 0.212 vs 4.994 ± 0.184 between 4 and 8 h after inducing pancreatitis).Melatonin protects rats against acute pancreatitis-associated lung injury, probably through the upregulation of IL-22 and Th22, which increases the innate immunity of tissue cells and enhances their regeneration.