Extra-cellular signals, including T lymphoc ytes, cytokines,growth factors,interferons and neuropeptides, which could modulate matrix metalloproteinases expression in synoviocytes of rheumatoid arthritis(RA), are often mediated by G-protein-coupled Receptors (GPCR)-initiated signaling and mitogen-activated protein kinase (MAPK) cascades. Drug targets which aim at the extra-cellular signals or intra-cellular cascades is required for ameliorating inflammatory reaction and preventing joint destruction in RA.

The activation of MAPKs signal transduction parthways, is a typical feature of chronic synovitis in rheumatoid arthritis. The phosphorylation of synoviocytes cytoplasm proteins induced transcription factor and nucleus proteins phosphorylation such as c-fos, c-jun, AP-1 and NF-?B via MAPKs signal transduction, which promotes synoviocytes proliferation and activation. These findings may be beneficial for the elucidation of the pathogenesis and the development of new drugs for rheumatoid arthritis.

Aim To investigate the effects and mechanisms of glucosides of chaenomeles speciosa (GCS) in mice with contact hypersensitivity (CHS) response. Methods CHS model in mice induced by 2,4-dinitro-I-dinitroflurobenzene (DNFB) was used in this study. Concanavalin A (Con A)-induced splenocytes proliferation was measured by the MTT colorimetric method and interleukin-2 (IL-2) activity was measured by testing its ability to support ConA-induced mice splenocytes proliferation by MTT method. Interleukin-4 (IL-4) and transforming growth factor -beta 1 (TGF-? 1) levels were determined by ELISA. T lymphocytes subsets were measured by flow cytometry. Results Similar as the control drug 4-acetylaminophenylacetic acid (actarit or Acta) (120 mg?kg -1), GCS (240 mg?kg -1) could inhibit the thymus index and spleen index in CHS mice. GCS( 60,120,240 mg?kg -1) could inhibit the ear swelling of CHS mice and could inhibit the splenocytes proliferation induced by ConA. GCS (240 mg?kg -1)decreased CD4 +CD8 +T lymphocytes subsets ratio and resumed the CD4 +CD8 -subsets ratio in CHS mice;GCS(240,60 mg?kg -1) resumed the CD4 -CD8 -subsets ratio in CHS mice. GCS also decreased the TGF-? 1 and IL-2 levels and increased the IL-4 levels in mice thymus with CHS. Conclusion GCS could inhibit mice CHS reaction and resume the balance of T lymphocytes subsets in mice thymus with CHS, and also could modulate the cytokines production by CD4 + T lymphocytes of CHS mice.

Objective To explore the application of high-frequency color Doppler in the diagnosis of infant intussusception and the selection of reduction mode according tO the hemodynamic situations of intussusception intestine tube and blood vessel in mesentery.Methods A total of 377 cases of doubtful intussusception infants wete checked by high-frequency color Doppler.After they had been diagnosed,the hemodynamic situations of intussuscepiton intestine tube and blood vessel in mesentery were carefully observed and the ultra-sound had 3 types and then the hydrostatic enema reduction was chosen as treatment method.Results A total of 263 cases was diagnosed by highfrequency colot Doppler with rate of coincidence of 100%.Among them are 253 successful cases reduced by hydrostatic enema.The successful rate of reduction was 96.2%and the 10 failed cases were changed to be treated bv operation.The intestinal wall of intussusception tube in failure group had serious dropsy without blood flow shown.Conclusions It is accurate that the infant intussusception is diagnosed by high-frequency color Doppler.According to the hemodynamic situations of intussusceptin intestine tube and blood vessel in mesentery,the infant intussusception can be divided into 3 types as follows:type Ⅰ:the blood signal of intestinal tube and wall is up or normal,which shall be reduced by hydrostatic enema;type Ⅱ:the blood signal of intestinal tube and wall is small with high obstruction index,which shall be reduced by hydrostatic enema as possible as it can;type Ⅲ:the intestinal wall has serious dropsy with rather high obstruction index and without blood flow shown,in which the hydrostatic enema redHetion shall bebanned and the operation shall be carried out as soon as possible.

Objective To explore the ultrasonographical characteristics of placental abruption, especially the light placental abruption that was diagnosed by color Doppler ultrasonic combining with enhancement Doppler E-flow imaging, providing diagnosis data for clinical treatment. Methods With color Doppler ultrasonic and enhancement Doppler E-flow imaging, an analysis was made on the ultrasonography and clinical result of 50 patients with heavy placental abruption and 23 patients with light placental abruption. Results The diagnosis and clinical treatment of 50 patients with heavy placental abruption who had been diagnosed by color Doppler ultrasonic combining with enhancement Doppler E-flow imaging were in conformity with the postnatal pathological diagnosis. The coincidence rate in diagnosis was 100%. Of 23 patients with light placental abruption who had been diagnosed by color Doppler ultrasonic combining with enhancement E-flow Doppler imaging, 19 cases' diagnosis and clinical treatment were in accordance with their postnatal pathological diagnosis and the coincidence rate was 83%, 4 cases were misdiagnosis and missed diagnosis. Of 73 patients with placental abruption, 60 cases were carried out caesarean birth and 13 cases performed natural labor. Conclusion The enhancement Doppler E-flow imaging combining with color Doppler ultrasonic can accurately diagnose the heavy placental abruption and also provide a new method for the diagnosis of light placental abruption and perform a dynamic monitoring for the treatment transfer result of it.

Objective To explore the improvement of cognitive impairment in patients with mild and moderate vascular cognitive impairment( VCI) treated with cerebralcare granule ( CG) and basic treat-ment.Methods From October in 2014 to December in 2016 year,143 cases of VCI patients were admitted from six hospitals in some areas of Hebei Province as the research objects,and divided into CG treatment group (experimental group,n=98) and conventional treatment group (control group,n=66).Three months and six months after treatment,the score of mental state examination ( MMSE) ,the Montreal cognitive assess-ment scale ( MoCA) and the daily living capacity scale( ADL) of the two groups were compared after 3 and 6 moths of treatment.Results ①The total score of MMSE in the experimental group was higher than that of the control group for six months after treatment, and the difference was statistically significant ( ( 23. 76 ± 4.02) vs (21.52±5.13),P<0.05).②Six months after treatment,the total score of MoCA ((21.06±4.66) vs (18.32±5.20)) and visual spatial/executive function((3.05±1.37) vs (2.42±1.66)),calculation force ((2.24±0.84) vs (1.83±1.05)) and orientation ability((5.20±1.12) vs (4.06±1.35)) scores in the ex-perimental group were significantly higher than those in the control group (P<0.05) .③Six months after treat-ment,the ADL score in the experimental group was lower than that before treatment,and the difference was statistically significant((24.96±8.74) vs (29.20±11.55),P<0.05);while there was no significant difference in the ADL score between the experimental group and the control group after 6 months (P>0.05).Conclusion CG can improve cognitive function in mild to moderate VCI patients,mainly in visual space/execution func-tion,calculation ability and orientation ability,and with the extension of treatment time,the curative effect is more obvious.

Objective To study the therapeutic value of endoscopy for primary duodenal lesions. Methods Data of 79 consecutive patients with primary duodenal lesions, who underwent endoscopic treatment from January 2015 to January 2018 at Beijing Friendship Hospital, were retrospectively analyzed. Patients were divided into the complication group and the non-complication group, and further grouped according to lesion locations and endoscopic categories. Baseline data of patients, endoscopic treatment, wound closure method, pathological results, the occurrence and outcome of complications were studied. Results A total of 79 patients successfully went through endoscopic treatment, including 59 cases of endoscopic mucosal resection ( EMR) , 5 cases of endoscopic submucosal dissection ( ESD) , 6 cases of full-thickness resection with OTSC metal clips, and 9 cases of endoscopic piecemeal mucosal resection ( EPMR) . In all 79 cases, complications occurred in 8 patients ( 10. 1％) during the perioperative period, all at the duodenal descending segment and duodenal papilla. In all 47 cases whose lesions located at duodenal papilla and duodenal descending segment, the complication incidence was 17. 0％ ( 8/47) , significantly higher than that of non-descending and papilla part [ 0 ( 0/32 ) , P=0. 012 ] . Two ( 2. 5％) cases had complications requiring further intervention with endoscopy or surgery. Among 8 patients with complications, 1 patient ( 2. 1％) developed intraoperative perforation, 1 patient ( 2. 1％) developed delayed bleeding, 6 patients ( 12. 8％) developed mild acute pancreatitis, and these 8 patients recovered after treatment. These 47 patients were further divided into the duodenoscopy group and the gastroscopy group according to endoscopic categories, the complications incidence in the duodenoscopy group ( 28. 0％, 7/25) was also significantly higher than that in the gastroscopy group [ 4. 5％( 1/22) , P=0. 037] . Conclusion Endoscopic treatment is safe and effective for primary duodenal lesions. But for the operations in the duodenal descending segment and the duodenal papilla, as well as in the case of duodenoscopy, it is necessary to be more vigilant about the occurrence of complications.

Objective:To evaluate the clinical efficacy of endoscopy for early cancer of duodenal papilla.Methods:A retrospective analysis was performed on data collected from 23 consecutive patients with early cancer of duodenal papilla, who underwent endoscopic treatment from January 2015 to January 2021 in Beijing Friendship Hospital. Baseline data, endoscopic and pathological data, occurrence and outcome of complications were studied.Results:Twenty-three patients successfully received endoscopic treatment. The maximal diameter of lesions evaluated under endoscopy was 1.90±0.83 cm. Among the 23 cases, 20 underwent endoscopic mucosal resection and 3 underwent endoscopic piecemeal mucosal resection. Delayed bleeding occurred in 5 cases (21.7%), 3 patients (13.0%) developed postoperative hyperamylasemia, 6 patients (26.1%) developed mild acute pancreatitis, and 1 patient (4.3%) had pancreatic duct stent displacement after the operation, which improved after medical or endoscopic treatment. No perforation occurred during the perioperative period. In terms of final pathology, the en bloc resection rate was 82.6% (19/23), and the complete resection rate was 78.3% (18/23). Preoperative endoscopic ultrasonography showed that 19 lesions were confined to the mucosal layer, which were all demonstrated by postoperative pathology. Four other cases were suspected to be involved in the submucosa or the end of the pancreaticobiliary duct under endoscopic ultrasonography, two of which were confined to the mucosal layer, and the other 2 cases involved the submucosal layer, so additional surgery was performed. A total of 18 patients were followed up, among whom 14 achieved complete resection of postoperative pathology, and 2 patients (14.3%, 2/14) were found to have recurrence at 12 and 51 months respectively after the treatment and did not relapse after surgical treatment and endoscopic treatment respectively. Among 4 other patients of follow-up whose pathology did not achieve complete resection, 1 had no recurrence, and the other 3 received additional surgical treatment without recurrence.Conclusion:Endoscopic treatment for early cancer of duodenal papilla is safe and effective. It is necessary to improve preoperative evaluation, stay alert to perioperative complications, and pay attention to regular postoperative endoscopic follow-up.

Objective:To evaluate the clinical efficacy of endoscopic treatment for early nonampullary duodenal cancer.Methods:Data of patients with early nonampullary duodenal cancer, who underwent endoscopic treatment from January 2015 to January 2021 at Beijing Friendship Hospital were retrospectively analyzed. Baseline data, endoscopic treatment methods, wound closure, pathology, the occurrence and outcome of complications of patients were studied.Results:A total of 47 patients who successfully went through endoscopic treatment were enrolled. Seventeen cases received endoscopic mucosal resection (EMR), 5 cases received endoscopic submucosal dissection (ESD), and 7 cases received ESD+EMR (hybrid ESD). Six cases were converted to hybrid ESD due to difficulty in ESD. Four cases received full-thickness resection with over-the-scope clip system (OTSC), and 8 cases received endoscopic piecemeal mucosal resection (EPMR). Among the 47 cases of early cancer, the en bloc resection rate was 83.0% (39/47), and the complete resection rate was 85.1% (40/47). Four patients (8.5%) had perforation which occurred at the duodenal descending part during the perioperative period, among whom, 2 patients (4.3%) recovered after endoscopic treatment, 2 others (4.3%) recovered after surgical intervention. There were no complications such as postoperative bleeding or infection during the perioperative period.Conclusion:Endoscopic treatment for early nonampullary duodenal cancer is safe and effective. A specific treatment plan can be selected according to the location, size and specific conditions of the lesion. For the operation of the descending part, it is necessary to be more vigilant to against the occurrence of perforation complications.

Objective: To assess the efficacy and safety of endoscopic piecemeal mucosal resection (EPMR) and endoscopic submucosal dissection (ESD) in the treatment of larger (≥10-15 mm) non-ampullary duodenal lesions. Methods: The data of 21 patients with larger (≥10-15 mm) non-ampullary duodenal lesions, who underwent EPMR or ESD in Beijing Friendship Hospital from February 2013 to August 2018 were retrospectively analyzed. According to the treatment plan, the patients were divided into the EPMR group (n=13) and the ESD group (n=8). The operation time, pathological histological evaluation and complications of each group were summarized. Results: In the EPMR group, all 13 lesions were originated from the mucosa. The diameter of the lesion estimated by endoscopy and the size of the resected specimen were 22±12 mm and 26±15 mm, respectively, the median operation time was 39.0 (23.0, 45.0) min, and 12 lesions were closed with metal clips. For pathological assessment, there were 2 cases of ectopia gastric mucosa, 7 cases of low grade intraepithelial neoplasia, and 4 cases of high grade intraepithelial neoplasia. And 5 cases were horizontal margin positive (low grade intraepithelial neoplasia) in the 13 lesions. Complications occurred in 2 patients, including 1 case of perioperative bacteremia, which was cured after anti-infective treatment, and another case of intraoperative perforation, which was recovered after emergency surgery. In the ESD group, there were 6 mucosal lesions and 2 submucosal lesions. The diameter of the lesion estimated by endoscopy and the size of the resected specimen were 17±5 mm and 20±7 mm, respectively, the median operation time was 47.5 (34.0, 68.0) min, and all 8 lesions were closed with metal clips. For pathological assessment, there were 3 cases of low grade intraepithelial neoplasia, 3 cases of high grade intraepithelial neoplasia, 1 case of submucosal cyst, and 1 case of lymphangioma. All 8 cases were horizontal margin negative, and low-grade intraepithelial neoplasia was suspected at the vertical margin of 1 case, which failed to achieve complete resection. Perioperative perforation occurred in 3 cases. One case recovered after endoscopic treatment, another case was unsatisfactory under endoscopy, and recovered after emergency surgery. The other case was recovered after laparoscopic treatment. Conclusion EPMR and ESD are both safe and effective for larger non-ampullary duodenal lesions, which is worthy of further clinical research.