In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.
Rats ; Animals ; Periploca ; Cysteine ; Cytidine Diphosphate Choline ; Network Pharmacology ; Phosphorylcholine ; Metabolomics ; Arthritis, Rheumatoid/drug therapy* ; Biomarkers ; Glycerophospholipids ; Methionine ; Purines ; Chromatography, High Pressure Liquid

OBJECTIVE: To explore the role of 5-hydroxytryptamine (5-HT) in type 2 diabetes mellitus (T2DM)-related hepatic inflammation and fibrosis. METHODS: Male C57BL/6J mice were used to establish T2DM model by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. Then, the mice with hyperglycemia were still fed with high-fat diet for nine weeks, and treated with or without 5-HT_2A receptor (5-HT_2AR) antagonist sarpogrelate hydrochloride (SH) and 5-HT synthesis inhibitor carbidopa (CDP) (alone or in combination). To observe the role of 5-HT in the myofibroblastization of hepa-tic stellate cells (HSCs), human HSCs LX-2 were exposed to high glucose, and were treated with or without SH, CDP or monoamine oxidase A (MAO-A) inhibitor clorgiline (CGL). Hematoxylin & eosin and Masson staining were used to detect the pathological lesions of liver tissue section, immunohistochemistry and Western blot were used to analyze protein expression, biochemical indicators were measured by ELISA or enzyme kits, and levels of intracellular reactive oxygen species (ROS) were detected by fluorescent probe. RESULTS: There were up-regulated expressions of 5-HT_2AR, 5-HT synthases and MAO-A, and elevated levels of 5-HT in the liver of the T2DM mice. In addition to reduction of the hepatic 5-HT levels and MAO-A expression, treatment with SH and CDP could effectively ameliorate liver lesions in the T2DM mice, both of which could ameliorate hepatic injury and steatosis, significantly inhibit the increase of hepatic ROS (H₂O₂) levels to alleviate oxidative stress, and markedly suppress the production of transforming growth factor β1 (TGF-β1) and the development of inflammation and fibrosis in liver. More importantly, there was a synergistic effect between SH and CDP. Studies on LX-2 cells showed that high glucose could induce up-regulation of 5-HT_2AR, 5-HT synthases and MAO-A expression, increase intracellular 5-HT level, increase the production of ROS, and lead to myofibroblastization of LX-2, resulting in the increase of TGF-β1 synthesis and production of inflammatory and fibrosis factors. The effects of high glucose could be significantly inhibited by 5-HT_2AR antagonist SH or be markedly abolished by mitochondrial 5-HT degradation inhibitor CGL. In addition, SH significantly suppressed the up-regulation of 5-HT synthases and MAO-A induced by high glucose in LX-2. CONCLUSION Hyperglycemia-induced myofibroblastization and TGF-β1 production of HSCs, which leads to hepatic inflammation and fibrosis in T2DM mice, is probably due to the up-regulation of 5-HT_2AR expression and increase of 5-HT synthesis and degradation, resulting in the increase of ROS production in mitochondria. Among them, 5-HT_2AR is involved in the regulation of 5-HT synthases and MAO-A expression.
Male ; Mice ; Humans ; Animals ; Hepatic Stellate Cells/pathology* ; Transforming Growth Factor beta1/pharmacology* ; Serotonin/metabolism* ; Reactive Oxygen Species/metabolism* ; Diabetes Mellitus, Type 2/complications* ; Hydrogen Peroxide/metabolism* ; Mice, Inbred C57BL ; Liver Cirrhosis/etiology* ; Hyperglycemia/pathology* ; Monoamine Oxidase/metabolism* ; Inflammation ; Glucose/metabolism* ; Cytidine Diphosphate/pharmacology*

Recombinant human growth hormone (rhGH) administration stimulate the secretion of the brain insulin-like growth factor-1 (IGF-1) concentration and IGF-1 is a pleiotropic neurotropic peptide to exert beneficial effect for the injured brain tissues. Citicoline (cytidine-59-diphosphocholine; CDP-choline) is well known to improve neurological outcome in acute stroke. This study aimed to evaluate whether rhGH can potentiate citicoline effect on functional recovery in acute stroke patient. Thirty patients were enrolled. Ten patients were treated with rhGH subcutaneous injection for 6 months on top of citicoline for 6 weeks (GH6 group), and 10 patients for 3 months (GH3 group) with 6 weeks of citicoline treatment as well, and final 10 patients only with citicoline (control group). Functional outcome was determined by Korean modified Barthel Index (K-MBI) and modified Rankin Scale (mRS) at baseline and 6 months after treatment. Seven and 4 patients withdrew from GH6 and GH3 group, respectively. Final 3 patients in GH6 group, 6 patients in GH3 group and 10 patients in control group were analyzed. The K-MBI, and mRS scores from all 3 groups increased in 6 months compared to baseline in intra-group comparison. In inter-group comparison, however, GH6 but not GH3 showed statistically significant improvement compared to control. Administration of rhGH for 6 months on top of 6-week citicoline treatment resulted in further improvement in K-MBI and mRS in acute stroke patients. Further studies in increasing injection dose or injection period is needed.
Brain ; Cytidine Diphosphate Choline ; Human Growth Hormone* ; Humans* ; Injections, Subcutaneous ; Insulin-Like Growth Factor I ; Stroke*

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the usefulness of computerized dynamic posturography (CDP) in patients with acute vestibular neuritis (AVN) by identifying the recovery period of Sensory Organization Test (SOT) and comparing the result of SOT with those of the vestibulo-ocular reflex (VOR) tests and subjective symptoms. SUBJECTS AND METHOD: A prospective study was conducted on 41 patients who were diagnosed with AVN. The SOT was measured daily until the equilibrium composite score recovered the normal value. A survey, composing of questionnaires on Visual Analogue Scale (VAS), Dizziness Handicap Inventory (DHI), motion sensitive quotient (MSQ) and Activities-Specific Balance Confidence Scale (ABC), was conducted on the patient's initial visit and on the day the normal value of SOT was recovered. Videonystagmography and the caloric test were also performed, and the results were compared with those of the SOT. RESULTS: The mean duration from the onset of vertigo to the recovery of SOT scores was 3.7±2.9 days (median 3.0 days) and that from the onset of vertigo to the disappearance of spontaneous nystagmus was 17.1±27.2 days (median 6.0 days). The scores of 4 questionnaires (VAS, DHI, MSQ, and ABC) were significantly different between the initial day and the day of recovery to the normal value of SOT (p<0.001). However, the velocity of spontaneous nystagmus on the initial visit and the degree of canal paresis from the caloric test showed no significant correlations to recovery duration from the onset of vertigo to the normalization of SOT score. CONCLUSION: The recovery duration of vestibulospinal reflex (VSR) is much shorter than that of VOR in patients with AVN. The recovery of subjective symptoms showed close correlation with the recovery of VSR, but the results of VSR was not correlated with that of VOR. Therefore, CDP could be a very useful test for monitoring the resolution of subjective symptoms in patients with AVN.
Caloric Tests ; Compensation and Redress* ; Cytidine Diphosphate ; Dizziness ; Humans ; Methods ; Paresis ; Prospective Studies ; Reference Values ; Reflex ; Reflex, Vestibulo-Ocular ; Vertigo ; Vestibular Neuronitis*

This study was to evaluate the efficacy and safety of early application of citicoline in the treatment of patients with acute stroke by meta-analysis. Randomized controlled trials published until May 2015 were electronically searched in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, WHO International Clinical Trial Registration Platform, Clinical Trial.gov, and China Biology Medicine disc. Two reviewers independently screened the articles and extracted the data based on the inclusion and exclusion criteria. The quality of included articles was evaluated by using Revman5.0, and meta-analysis was performed. The results showed that 1027 articles were obtained in initial retrieval, and finally 7 articles, involving a total of 4039 cases, were included for analysis. The meta-analysis showed that no significant differences were found in the long-term mortality (OR=0.91, 95% CI 0.07 to 1.09, P=0.30), the rate of dependency (OR=1.02, 95% CI 0.87 to 1.24, P=0.85), and the effective rate (OR=0.98, 95% CI 0.84 to 1.14, P=0.82) between citicoline group and control group. The overall rate of adverse events in citicoline group was not significantly different from that in control group (P=0.30). The quality of included articles reached moderate-low level. In conclusion, citicolne cannot reduce long-term mortality and dependence rate in the treatment of acute stroke, and the effective rate of citivoline may be not better than that of controls but with reliable safety.
Aged ; Cytidine Diphosphate Choline ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Nootropic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Randomized Controlled Trials as Topic ; Stroke ; drug therapy

OBJECTIVES: This study aims to determine the sensitivity, specificity, positive predictive value and negative  predictive  value  of  Computerized  Dynamic  Posturography  (CDP)  in  properly  labeling patients with peripheral vestibular disorders by Videonystagmography (VNG) as having vestibular dysfunction.
METHODS:
Design: Case - Control Study
Setting: Tertiary Private Hospital
Subjects: Twenty-three (23) patients aged 18 and above with no history of hypertension or cardiovascular disease and no intake of anti-vertigo medications for at least 48 hours prior to testing and with complete VNG and CDP results obtained on the same day or at least  two  days  apart  were  included  in  the  study. Cases were defined as those  diagnosed with a peripheral  vestibular  disorder  by VNG  while  controls  were  defined as those with  normal VNG results.  Sensitivity, specificity, positive predictive value and negative  predictive value of CDP in labeling those with peripheral vestibular disorders as vestibular were determined using VNG as gold standard.
RESULTS: There were 11 cases  (4  males, 7 females) and 12 controls (8  males,  4  females).  Using VNG  as  the  gold  standard  for  diagnosing  peripheral  vestibular  disorders,  CDP  had  a  sensitivity of 45.45% and specificity of 66.67% with Positive Predictive Value(PPV) of 55.56% and Negative Predictive Value(NPV) of 57.14%  in  assessing  peripheral vestibular disorders among the adults tested.  Interestingly, 33.33% of patients with normal VNG may actually have had a vestibular dysfunction that could be detected by CDP.
CONCLUSION: Prospective studies with larger sample sizes utilizing VNG and CDP are recommended in order to verify our findings.

Human ; Male ; Female ; Middle Aged ; Adult ; Adolescent ; Vertigo ; Vestibular Diseases ; Vestibule, Labyrinth ; Sensitivity And Specificity ; Cardiovascular Diseases ; Hypertension ; Hospitals, Private ; Cytidine Diphosphate

PURPOSE: To evaluate the clinical outcomes of patients with refractive aspheric multifocal intraocular lens (IOL) (Lentis Mplus(R) LS-313) implantation. METHODS: Sixty-eight eyes of 53 patients received refractive aspheric multifocal IOL implantation. Uncorrected visual acuity (UCVA) at a long distanc, as well as intermediate and near distances were measured on the first day, after two weeks, and during the first, third and sixth months postoperatively. Optical quality was evaluated using the Optical Quality Analysis System II (OQAS II). High-order aberrations (HOA) and patient satisfaction questionnaires were evaluated at three months post-operation. RESULTS: At the six-month postoperative visit, the mean UCVA at a long, two intermediate (63 cm, 100 cm) and a near distance were 0.06 +/- 0.07, 0.18 +/- 0.14, 0.15 +/- 0.13 and 0.11 +/- 0.10 log MAR, respectively. The means of the objective scatter index, modulation transfer function (MTF) cut off value, Strehl ratio and pseudo-accommodation range measured by OQAS II were 1.20 +/- 0.69, 34.15 +/- 9.53 cdp, 0.17 +/- 0.05 and 3.09 +/- 0.25 D, respectively. HOA of 5 mm and 6 mm were each 0.61 +/- 0.14 and 1.07 +/- 0.20, respectively. Eighty-two percent of patients were satisfied with the postoperative results, and 71% of the patients reported that they would recommend the procedure to others, while 24% of patients reported moderate or severe visual disturbance at night. CONCLUSIONS: Implantation of the refractive aspheric multifocal IOLs in patients with cataracts provided excellent distant, intermediate, and near visual outcomes and high patient satisfaction as well as presbyopia correction.
Cataract ; Cytidine Diphosphate ; Humans ; Lenses, Intraocular ; Patient Satisfaction ; Presbyopia ; Surveys and Questionnaires ; Visual Acuity

PURPOSE: To evaluate the clinical outcomes of patients with diffractive multifocal toric intraocular lens (IOL) implantation. METHODS: Thirty-four eyes of 26 patients underwent diffractive multifocal toric IOL. Uncorrected visual acuity (UCVA) at distant, intermediate and near and residual refractive astigmatism were measured on the first day, at 2 weeks, and 1, 3 and 6 months postoperatively. Optical quality obtained using the Optical Quality Analysis System II (OQAS II), high-order aberrations (HOA) and patient satisfaction questionnaire were evaluated 3 months postoperatively. RESULTS: At the 6 month postoperative visit, the mean UCVA at distant, intermediate (63 cm, 100 cm) and near were 0.06 +/- 0.07, 0.18 +/- 0.11, 0.16 +/- 0.12 and 0.03 +/- 0.06 (log MAR), respectively. The refractive astigmatism decreased significantly from -1.66 +/- 1.04 D to -0.54 +/- 0.32 D at 6 months postoperatively (p < 0.01). The means of objective scatter index, modulation transfer function (MTF) cut-off value, Strehl ratio and pseudo-accommodation range measured by OQAS II were 1.33 +/- 0.67, 37.24 +/- 9.67 cdp, 0.22 +/- 0.09 and 3.08 +/- 0.53 D, respectively. HOA scores for 5 mm and 6 mm were 0.30 +/- 0.09 and 0.49 +/- 0.15, respectively; 82.3% of the patients were satisfied with the postoperative results, 79.4% of the patients reported they would recommend the procedure to others, and 14.7% of patients reported moderate or severe visual disturbance at night. CONCLUSIONS: Implantation of a diffractive multifocal toric IOL in patients with cataract and corneal astigmatism provided excellent distant, intermediate, and near visual outcomes, good optical quality and high patient satisfaction.
Astigmatism ; Cataract ; Cytidine Diphosphate ; Humans ; Lens Implantation, Intraocular* ; Lenses, Intraocular ; Patient Satisfaction ; Surveys and Questionnaires ; Visual Acuity

OBJECTIVES: Depressive disorder (DD) is a complex disease, and the assessment of work ability in patients with DD is also complicated. The checklist depression (CDp) has recently been developed to support such work ability assessments and has been recommended for implementation in insurance medicine, starting with an analysis of the organisational and social contexts. The aim of this study was to identify the potential facilitators and barriers in the use of the CDp by insurance physicians (IPs) during work ability assessments of employees on sick leave due to DD. METHODS: A qualitative research was conducted based on semi-structured interviews. The participants were IPs with at least one year of work experience in performing work ability assessments. The interviews were audiotaped, transcribed and analysed qualitatively. RESULTS: Ten IPs (7 males, 3 females; mean 53 years) were interviewed. Important facilitators, which emerged for use of the CDp, were an oral introduction for colleagues and staff, support from management, valuing the increased transparency in work ability assessments with using the CDp, having adequate time for assessments as well as modification of the appearance (colour, plasticised form) and content (clarifying aspects of the examples) of the assessment tool. The fear of the loss of autonomy, lack of added value of the CDp, high workload, inadequate instructions and lack of time were mentioned as barriers. CONCLUSION: Adequate introduction to the use of CDp and the fear of the loss of autonomy of IPs need special attention in planning its implementation.
Checklist ; Cytidine Diphosphate ; Depression ; Depressive Disorder ; Depressive Disorder, Major ; Humans ; Insurance ; Male ; Occupational Medicine ; Qualitative Research ; Sick Leave

BACKGROUND AND PURPOSE: Cerebral white matter (WM) lesions are frequently observed in human cerebrovascular diseases, and are believed to be responsible for cognitive impairment. Various neuroprotective agents can suppress this type of WM or neuronal damage. In this study, we investigated whether citicoline, a drug used to treat acute ischemic stroke, can attenuate WM lesions and cognitive decline caused by chronic hypoperfusion in the rat. METHODS: Animals were divided into immediate- and delayed-treatment groups. Those in the immediate-treatment group received a sham operation, citicoline (500 mg/kg/day), or phosphate buffered saline (PBS) treatment. Citicoline or PBS was administered intraperitoneally for 21 days after occluding the bilateral common carotid arteries. Rats in the delayed-treatment group were intraperitoneally administered with either 500 mg/kg/day citicoline or PBS for 21 days beginning on the 8th day after the operation. From the 17th day of administration, the rats were placed in an eight-arm radial maze to examine their cognitive abilities. After completing the administration, tissues were isolated for Kluver-Barrera and the terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL) staining. RESULTS: In the immediate-treatment group, cognitive functions were preserved in the citicoline-treated group, and WM damage and TUNEL-positive cells differed significantly between the citicoline- and PBS-treated animals. In the delayed-treatment group, there was no decrease in WM damage and TUNEL-positive cells, but cognitive improvement was evident for citicoline treatment relative to PBS treatment. CONCLUSIONS: These results show that citicoline can prevent WM damage and aid cognitive improvement, even after a certain extent of disease progression. Citicoline might be useful in patients with acute ischemic stroke as well as in chronic stroke accompanied with cognitive impairment.
Animals ; Carotid Artery, Common ; Cytidine Diphosphate Choline ; Disease Progression ; DNA Nucleotidylexotransferase ; Humans ; Neurons ; Neuroprotective Agents ; Rats ; Salicylamides ; Stroke