Objective To study the influence of guiding herb of Radix Achyranthis Bidentatae(RAB) on therapeutic effect of diclofenac sodium for rats with adjuvant arthritis(AA) and its possible mechansim,and to further explore the pharmacodynamic and pharmacokinetic changes after using diclofenac sodium together with RAB.Methods Forty-five Wistar rats were equally divided into 5 groups:normal group,model group,RAB(RAB water extract 5.0 g?kg-1) group,diclofenac sodium(10 mg?kg-1) group,and the combination group.The rat model was induced by Freud's complete adjuvant.The foot edema was tested by volume method.HPLC was used to determine the diclofenac sodium concentration in foot tissue,and ELISA and radioimmunoassay method were used to determine PGE2 and IL-1?levels in vivo.Results In the combination group,the anti-inflammatory action was superior to that in diclofenac sodium group(P

Objective To investigate the efficacy evaluation of early continuous renal replacement therapy (CRRT) for severe acute pancreatitis in intensive care unit (ICU).Methods Prospective study was performed for 84 patients with severe acute pancreatitis admitted to the Xinjiang Provincial People's Hospital from June 2015 to March 2017.Those patients were divided into two groups by computer random coding:42 cases treated with CRRT (observation group), and 42 cases received routine treatment (control group).Statistically analysis was carried out between two groups regarding curative effect, symptom improvement, ICU hospitalization time, and serum markers before and after treatment.Results The total ef fective rate was 92.86 ％ in the observation group, and 85.71％ in the control group, without significant difference between two groups (F =0.516, P =0.632).Patients with symptoms, vital signs stable time, gastrointestinal function recovery time, and hospitalization time of ICU were significantly lower in the observation group than the control group [(3.16 ± 1.28) days:(5.21 ± 1.45) days, t =3.518, P =0.017, (2.55 ± 1.36) days:(4.34 ± 1.51) days, t =2.519, P =0.034, (4.46 ± 1.28) days:(6.28 ± 1.51) days, t=2.685,P=0.028, (15.06±2.24)days:(19.34 ±3.28) days, t=6.983, P=0.009].There is no significant differences in amylase (AMS), interleukin (IL)-6, C-reaction protein (CRP), tumor necrosis factor (TNF)α, prothrombin time (PT) and fibrinogen (FIB) before treatment between two groups (P ＞ 0.05).The observation group were significantly lower than the control group in AMS, IL-6, CRP, TNF-α, PT, and FIB levels after treatment [(206.59 ± 19.51) U/L:(258.12 ± 22.43) U/L, t =11.234, P=0.001, (34.58 ±6.41)ng/L:(41.36 ± 8.52) ng/L, t =4.121,P =0.013, (88.24 ± 6.95) ng/L:(104.33 ±10.82) ng/L, t=8.109,P=0.002, (178.35 ±27.43)pg/ml:(249.28 ±34.33)pg/ml, t=7.384,P=0.007, (12.48±3.54)s:(14.56 ±4.62)s, t =6.473,P=0.011, (3.38±1.55)g/L:(4.57 ± 2.86)g/L, t =4.108, P =0.041].Two groups of patients after treatment were cured, and no serious complications occurred during hospitalization.Conclusions For patients with severe acute pancreatitis, the overall effective rate of CRRT in ICU was high, the clinical symptoms relieved quickly, the level of serum indicators improved effectively.

Objective To investigate the expression of miRNA-31 in peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients,and the relationship between miRNA-31 and disease activity of RA.Methods After obtaining the informed consent,peripheral blood samples of 56 RA patients,12 systemic lupus erythematosus (SLE) patients,6 Sj(o)gren's syndrome (SS) patients and 30 healthy controls were collected from the Department of Rheumatology,Peking University Third Hospital.RNA was extracted from the PBMCs which were separated by Ficoll-Paque PLUS.The expression of miRNA-31 in the PBMCs of RA patients,SLE patients,SS patients and healthy controls was detected by real-time Polymerase Chain Reaction (PCR).Furthermore,according to the RA disease activity score (DAS28),RA patients were divided into high,moderate and low disease activity groups and remission group,and miRNA-31 expression was compared between different groups.Data were analyzed using t test or Mann-Whitney U test.Results The expression of miRNA-31 in PBMCs of RA patients was 7.25 times (P=0.003 8) higher when compared with that of the control group.To be specific,the expression of miRNA-31 was 10.63 times in PBMCs of high activity RA group (P=0.01) and 8.95 times in moderate activity RA group (P=0.000 3) when compared with that of the control group,and there was no significant difference between low activity,remission groups and control groups in terms of miRNA-31 expression.Furthermore,the expression of miRNA-31 in PBMCs of SLE patients was not significantly different from the control and miRNA-31 expression in PBMCs of SS patients was 1.64 times (P=0.02) higher than that of the RA patients,but the average level of miRNA-31 was much less than that of RA patients.The increased miRNA-31 may serve as a diagnostic marker for disease activity of RA.

Objective To investigate the potential mechanism of circRNA SAMD8(circ-SAMD8)in development of pancreatic ductal adenocarcinoma(PDAC).Methods The expression profile of circRNAs in PDAC tissues was analyzed based on Microarray data(GSE79634).Quantita-tive real-time polymerase chain reaction(qRT-PCR)was used to verify the expression of circ-SAMD8(hsa_circ_0006148)in PDAC tissues and cells(CFPAC-1 and PANC-1).The target microRNA(miRNA)of circ-SAMD8 and its downstream mRNA were predicted by bioinformatics analysis,and identified by double luciferase reporter gene assay.The proliferation ability of PDAC cells was detec-ted by MTT assay and colony formation assay.The expression levels of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax were detected by Western blot.The percentage of apoptotic cells was detected by flow cytometry.Results The expression levels of circ-SAMD8 in PDAC tissues and cells were significantly lower than those in paracancer tissues and normal cells(P＜0.05).Overexpression of circ-SAMD8 could effectively promote apoptosis of PDAC cells and inhibited proliferation of PDAC cells.Dual luciferase reporter gene experiments showed that miR-223-3p was a potential interacting mol-ecule of circ-SAMD8,and the downstream mRNA target of miR-223-3p was RHOB.The miR-223-3p was abnormally overexpressed in PDAC tissues and cells,accompanied by low RHOB expression.In PDAC cells transfected with miR-223-3p mimics or sh-circ-SAMD8,RHOB expression was significantly decreased,proliferation ability was enhanced,and apoptosis rate was decreased.Conclusion Circ-SAMD8 regulates the expression of RHOB downstream by sponging miR-223-3p,and effectively inhibits the occurrence and development of PDAC.

Objective To investigate the potential mechanism of circRNA SAMD8(circ-SAMD8)in development of pancreatic ductal adenocarcinoma(PDAC).Methods The expression profile of circRNAs in PDAC tissues was analyzed based on Microarray data(GSE79634).Quantita-tive real-time polymerase chain reaction(qRT-PCR)was used to verify the expression of circ-SAMD8(hsa_circ_0006148)in PDAC tissues and cells(CFPAC-1 and PANC-1).The target microRNA(miRNA)of circ-SAMD8 and its downstream mRNA were predicted by bioinformatics analysis,and identified by double luciferase reporter gene assay.The proliferation ability of PDAC cells was detec-ted by MTT assay and colony formation assay.The expression levels of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax were detected by Western blot.The percentage of apoptotic cells was detected by flow cytometry.Results The expression levels of circ-SAMD8 in PDAC tissues and cells were significantly lower than those in paracancer tissues and normal cells(P＜0.05).Overexpression of circ-SAMD8 could effectively promote apoptosis of PDAC cells and inhibited proliferation of PDAC cells.Dual luciferase reporter gene experiments showed that miR-223-3p was a potential interacting mol-ecule of circ-SAMD8,and the downstream mRNA target of miR-223-3p was RHOB.The miR-223-3p was abnormally overexpressed in PDAC tissues and cells,accompanied by low RHOB expression.In PDAC cells transfected with miR-223-3p mimics or sh-circ-SAMD8,RHOB expression was significantly decreased,proliferation ability was enhanced,and apoptosis rate was decreased.Conclusion Circ-SAMD8 regulates the expression of RHOB downstream by sponging miR-223-3p,and effectively inhibits the occurrence and development of PDAC.

Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; Escherichia coli ; genetics ; metabolism ; Escherichia coli Proteins ; chemistry ; genetics ; metabolism ; Models, Molecular ; N-Acetylgalactosaminyltransferases ; chemistry ; genetics ; metabolism ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Substrate Specificity

Objective:To investigate the effects of compound Duzhong Jiangu Granules on joint function and gut microbiota in patients with Kashin-Beck disease.Methods:A single group pre- and post-experimental design was conducted, the patients with Kashin-Beck disease were selected as the subjects in Xunyi County, Xianyang City, Shaanxi Province; and treated with oral administration of compound Duzhong Jiangu Granules (12 g/bag, 1 bag/time, 3 times/day) for a period of 1 month. The improvement of joint function was evaluated using the joint dysfunction index scoring method before and after treatment. Morning stool samples of patients were collected and the changes in gut microbiota were analyzed before and after treatment using 16S rDNA sequencing technology.Results:A total of 87 patients with Kashin-Beck disease were included, including 44 males and 43 females; the age was (60.38 ± 7.12) years old, and the body mass index was (23.67 ± 3.59) kg/m 2. The comprehensive scores of joint dysfunction index for patients with Kashin-Beck disease before and after treatment were (7.27 ± 2.05) and (5.86 ± 2.01) points, respectively, and the difference was statistically significant ( t = 5.88, P < 0.001). The sequencing results of gut microbiota showed that there were statistically significant differences in the alpha diversity (chao1, observed species index) and beta diversity of gut microbiota in patients with Kashin-Beck disease before and after treatment ( Z = - 5.08, - 5.03, R = 0.09, P < 0.001). In the distribution of gut microbiota, Firmicutes was the dominant phylum, with relative abundances of 50.21% and 52.09% before and after treatment, respectively; the Bifidobacterium was the dominant bacterial genus, with relative abundances of 16.83% and 18.81% before and after treatment, respectively. At the genus level, a total of 17 gut microbiota genera were screened out, among which the relative abundances of Hafnia-Obesumbacterium, Gammaproteobacteria_unclassified, Acinetobacter, Pantoea, Leuconostoc, and Akkermanisia were significantly higher than before treatment ( Z = - 2.40, - 2.24, - 2.06, - 3.59, - 2.24, - 2.11, P < 0.05). The relative abundances of Dubosiella, Selenomonas, Anaeroplasma, Lachnospiraceae_ NK4A136_group, Rikenella, Prevotella, Megasphaera, Lactobacillus, Prevotella-9, Phascolarctobacterium, and Desulfovibrio were significantly lower than before treatment ( Z = - 9.38, - 2.61, - 2.18, - 8.43, - 2.45, - 2.46, - 2.49, - 7.29, - 2.29, - 2.55, - 2.08, P < 0.05). Conclusions:Compound Duzhong Jiangu Granules can effectively improve the joint function of patients with Kashin-Beck disease, and alter the diversity and richness of the gut microbiota community. It may reduce clinical symptoms in patients by regulating the structure of gut microbiota.

Adenosine is a metabolite produced abundantly in the tumor microenvironment, dampening immune response in inflamed tissues via adenosine A2A receptor (A2AR) which is widely expressed on immune cells, inhibiting anti-tumor immune response accordingly. Therefore, blocking adenosine signaling pathway is of potential to promote anti-tumor immunity. This review briefly introduces adenosine signaling pathway, describes its role in regulating tumor immunity and highlights A2AR blockade in cancer therapy. Prospective anti-tumor activity of adenosine/A2AR inhibition has been revealed by preclinical data, and a number of clinical trials of A2AR antagonists are under way. Primary results from clinical trials suggest that A2AR antagonists are well tolerated in cancer patients and are effective both as monotherapy and in combination with other therapies. In the future, finding predictive biomarkers are critical to identify patients most likely to benefit from adenosine pathway blockade, and further researches are needed to rationally combine A2AR antagonists with other anti-tumor therapies.
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Adenosine/therapeutic use* ; Adenosine A2 Receptor Antagonists/therapeutic use* ; Humans ; Lung Neoplasms ; Receptor, Adenosine A2A/metabolism* ; Tumor Microenvironment

Animals ; Centromere ; metabolism ; Chromosomal Proteins, Non-Histone ; metabolism ; Mice ; Models, Molecular ; Synaptonemal Complex ; metabolism

BACKGROUND: Low dose computed tomography (LDCT) for lung cancer screening is widely employed in China as a result of increasing cancer screening awareness. Although some pulmonary lesions detected by LDCT are cancerous, most of the pulmonary nodules are benign. It is important to make effective preoperative differentiation of pulmonary lesions and to obviate the need for surgery in some patients with benign disease. METHODS: From January 1, 2017 to December 31, 2018, patients in our institution with surgical pathology confirmed benign pulmonary lesions in which malignancy could not be excluded in preoperative assessment were enrolled in this study. Retrospective analysis of clinical data was conducted. RESULTS: 297 cases were collected in this study. Prevalence of benign disease in patients underwent resection for focal pulmonary lesions is 9.8% in our institution. In 197 patients (66.3%), pulmonary lesions were detected by LDCT screening. A total of 323 assessable pulmonary lesions were detected by chest CT. The average diameter of pulmonary lesions was (17.9±12.1) mm, and 91.0% of which were greater than or equal to 8 mm. Solid nodules accounted for 65.6% of these lesions. Imaging characteristics suggesting malignancy were common, including spicule sign (71/323, 22.0%), lobulation (94/323, 29.1%), pleural indentation (81/323, 25.1%), vascular convergence sign (130/323, 40.2%) and vacuole sign (23/323, 7.1%). 292 patients (98.3%) underwent video-assisted thoracoscopic surgery (VATS). Pulmonary wedge resection was performed in 232 cases (78.1%), segmental resection in 13 cases (4.4%) and lobotomy in 51 cases (17.2%). Surgical complications occurred in 4 patients (1.3%). The most frequent findings on surgical pathology analysis were: infectious lesions in 98 cases (33.0%), inflammatory nodules in 96 cases (32.3%), and hamartoma in 64 cases (21.5%). CONCLUSIONS Solid nodules accounted for most of these benign pulmonary lesions in which malignancy could not be excluded preoperatively, and imaging characteristics suggesting malignancy were common. VATS is an important biopsy method to identify etiology and pathology for lesions. The most frequent benign pulmonary diseases that are suspected to be malignant and underwent surgical resection are: infectious lesions, inflammatory nodules and hamartoma.