BACKGROUND: Chronic musculoskeletal pain can cause disability and decreased quality of life of patients. Probing into the therapeutic methods of musculoskeletal disease and choosing proper treatment drugs are important for patients.OBJECTIVE: To evaluate the efficacy and tolerance of controlled-release tramadol in patients with moderate to severe chronic pain of musculoskeletal origin.DESIGN: A self-control study was conducted.SETTING: Arthrtosis Institute, People' s Hospital Affiliated to Peking University.PARTICIPANTS: Patients who were in the Orthopaedic Outpatient Service,People' s Hospital of Peking University were involved. This observational study was conducted in 40 adults who experienced moderate to moderately severe chronic musculoskeletal pain that was not controlled by routine nonsteroidal anti-inflammatory drugs(NSAID) therapy.INTERVENTIONS: Any NSAIDs and other analgesics were prohibited. Patients initially took 50 mg of controlled-release tramadol (Tramcontin) every 12hours, supplemented by every 50 mg if insufficient pain relieved. Recommended daily maximum dose was 400 mg per day. The observation lasted for 4 weeks. The patients were asked for document therapy-relevant data every day and were interviewed every week to doctor assessment.MAIN OUTCOME MEASURES: Pain intensity before and after treatment, pain remission degree, all side effects and their severity.RESULTS: All cases were finished the study and no one withdrew from follow-up. No eligible patients exited from the study because of therapeutic failure or intolerance. In comparison with the initial visual analogue scale (VAS) mean value 6. 80 ± 1.84, the average VAS value at the end of observation was 1.00 ± 1.46, which had significant difference( P ＜ 0. 001) . An average pain reduction of (85. 50±5.35)%was obtained, among which 78% were absolutely and obviously lessened. Side effects were reported in 9cases (22%).Drowsiness and dizziness(6 cases) was the most common, followed by nausea (3 cases), vomiting (1 case), somnolence (2 cases), constipation and urinary retention (1 case) and blurred vision (1 case).CONCLUSION: Tramcontin, as slow-release tramadol, proved to be an effective, safe, and easy-to-use central acting analgesic has an important role in the management of chronic musculoskeletal pain. Light side effect and good tolerance has provided a new choice for treatment of chronic pain in the orthopaedic department.

To explore the relationship between blood level of big endothelin and contrast-induced acute kidney injury (CI-AKI) in patients with emergent percutaneous coronary intervention (PCI). Methods: A total of 1061 consecutive patients received emergent PCI in our hospital from 2013-01 to 2015-06 were enrolled. According to blood levels of big endothelin, the patients were divided into 2 groups: Normal big endothelin group, n=236 and Elevated big endothelin group, n=825. The baseline condition, procedural features, occurrence rate of CI-AKI and composite endpoint events at 6 and 12 months post-operation were studied which including nonfatal myocardial infarction, revascularization, stroke and all-cause death. The risk factors for CI-AKI occurrence were identified by Logistic analysis. Results: The overall occurrence rate of CI-AKI was 22.7% (241/1061). Compared with Normal big endothelin group, Elevated big endothelin group had the higher incidence of CI-AKI, increased composite endpoint events at 6 and 12 months post-operation with P=0.041, P=0.040 and P=0.021, respectively. With adjusted covariates, elevated blood level of big endothelin, no matter as a continuous variable or categorical variable had the enhanced risk of CI-AKI incidence in patients after emergent PCI. Conclusion: Elevated blood level of big endothelin may significantly increase the risk of CI-AKI in patients with emergent PCI.

Often, pathological Gleason Score (GS) and stage of prostate cancer (PCa) were inconsistent with biopsy GS and clinical stage. However, there were no widely accepted methods predicting upgrading and upstaging PCa. In our study, we investigated the association between serum testosterone and upgrading or upstaging of PCa after radical prostatectomy (RP). We enrolled 167 patients with PCa with biopsy GS ≤6, clinical stage ≤T2c, and prostate-specific antigen (PSA) <10 ng ml-1 from April 2009 to April 2015. Data including age, body mass index, preoperative PSA level, comorbidity, clinical presentation, and preoperative serum total testosterone level were collected. Upgrading occurred in 62 (37.1%) patients, and upstaging occurred in 73 (43.7%) patients. Preoperative testosterone was lower in the upgrading than nonupgrading group (3.72 vs 4.56, P< 0.01). Patients in the upstaging group had lower preoperative testosterone than those in the nonupstaging group (3.84 vs 4.57, P= 0.01). In multivariate logistic regression analysis, as both continuous and categorical variables, low serum testosterone was confirmed to be an independent predictor of pathological upgrading (P = 0.01 and P= 0.01) and upstaging (P = 0.01 and P = 0.02) after RP. We suggest that low serum testosterone (<3 ng ml-1 ) is associated with a high rate of upgrading and upstaging after RP. It is better for surgeons to ensure close monitoring of PSA levels and imaging examination when selecting non-RP treatment, to be cautious in proceeding with nerve-sparing surgery, and to be enthusiastic in performing extended lymph node dissection when selecting RP treatment for patients with low serum testosterone.

Puerarin (PUE), as an isoflavone component, has a wide range of pharmacological activities, while its poorly aqueous solubility limits the development of solid oral dosage forms. In this study, PUE along with nicotinamide (NIC) were prepared into the coamorphous system by solvent-evaporation method and characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). In addition, its dissolution behavior and solubilization mechanism were also investigated. PUE-NIC coamorphous was a single homogeneous binary system, with a single glass transition temperature at 35.1 ℃. In comparison to crystalline PUE, during the dissolution process, coamorphous PUE-NIC not only exhibited the "liquid-liquid phase separation" (LLPS) phenomenon, but the formation of A_p type complexation (1∶1 and 1∶2) between PUE and NIC molecules was also verified, which significantly improved the solubility of PUE and prolonged the supersaturation time, and would benefit its absorption.

ObjectiveTo investigate the effect of intensive insulin therapy in critically ill elderly patients.MethodsElderly patients ( ≥ 65 years) admitted to the ICU of Beijing Tongren Hospital from June 2005 to December 2007 were divided into Group A ( glucose control target was 4.4-6.1mmol/L) and Group B ( glucose control target was 7.3-8.3mmol/L).Blood glucose level was controlled with a computer-assisted glucose control protocoL ResultsA total of 639 patients were enrolled,of which 280 were in Group A and 359 in Group B.The mean blood glucose level of the 2 groups was (6.07 ± 0.56) mmol/L and (7.52 ± 0.87 ) mmol/L respectively,both within the target ranges.The hyperglycemic index was (0.69±0.44) mmol/L in Group A and ( 1.60 ±0.73) mmol/L in Group B (P =0.000).No hypoglycemia adverse events occurred in either group.No significant differences were observed in the length of stay in ICU,duration of mechanical ventilation,hospitalization expenses,ICU mortality,and hospital mortality of the 2 groups.ConclusionMaintaining the blood glucose level of critically ill elderly patients at ≤8.3 mmol/L is safe and practical.

Objective ， To investigate the role of serum chemokines and oxidative and antioxidant biomarkers in occupational （ silicosis） Methods silicosis hereinafter referred to as . A total of 58 patients with stage Ⅰ silicosis were selected as the - （ ）， research subjects using convenient sampling method. The serum levels of nuclear factor erythroid 2 related factor 2 Nrf2 -（ - ） - （ - - ） - heme oxygenase 1 HO 1 and 8 isoprstaglandin F2α 8 iso PGF2α were determined by enzyme linked immunesorbent assay. （ ） （ - ） The serum levels of lipid peroxide LPO and total antioxidant capacity TAOC were determined by chemistry colorimetric method. - - （ - ）， Luminex flow fluorescence technology was used to detect the serum levels of interferon γ inducible protein10 IP10 macrophage （ ）- ， - - （ ） inflammatory protein MIP 1α MIP1β and macrophagederived chemokine MDC . The above indicators were analyzed by factor Results - analysis. The information extraction rate of the original indicators of the nine biomarkers was 58.5%96.5%. Four common ， ， （ ） ， factors were extracted including Nrf2 antioxidant signaling pathway helper T cell Th 1 dominant chemotaxis the total ， ， ， ， ， oxidation/antioxidant balance and Th2 dominant chemotaxis whose variance contribution rates were 32.2% 19.1% 16.4% ， ， Conclusion - and 11.8% respectively and the cumulative variance contribution rate was 79.5%. Both the oxidant antioxidant ， disturbance and the dominance chemotaxis are involved in the occurrence and development of silicosis and the Nrf2 antioxidant signaling pathway plays the most critical role.

The paper reviewed compositions and pharmacological effects of eight antidiabetic herbal drugs that have been approved by health regulatory agency for commercial use in China. Investigators attributed the hypoglycemic effect of these products to their ability to restore the functions of pancreatic tissues and cause an increase in insulin output, to inhibit the intestinal absorption of glucose, or to the facilitation of metabolites in insulin-dependent processes. Treatment with herbal drugs has an effect on protecting beta cells and smoothing out fluctuations in glucose levels. The use of these naturally derived agents in conjunction with conventional drug treatments such as an chemical agent or insulin permits the use of lower doses of the drug and/or decreased frequency of administration which decreases the side effects most commonly observed.
Animals ; Astragalus Plant ; chemistry ; Blood Glucose ; metabolism ; Diabetes Mellitus ; drug therapy ; metabolism ; Drug Combinations ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Humans ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; therapeutic use ; Insulin Resistance ; Panax ; chemistry ; Phytotherapy ; Plants, Medicinal ; chemistry ; Rehmannia ; chemistry

To investigate the role and mechanism of ceramide (Cer) regulation in alcohol-induced neuronal proliferation and the newborn neurons formation, we used sphingomyelin synthase 2 (predominant enzyme of Cer metabolism) knockout (SMS2(-/-)) and wild type (WT) female mice to establish the model of prenatal alcohol exposure. In 24 h after being given birth (postnatal day 0, P0), the offspring of model mice received blood sphingomyelin (SM) measurement with enzymatic method. On P0, P7, P14 and P30, the proliferation of granule cells in the dentate gyrus and newborn neurons were investigated with immunofluorescent labeling. The expression of protein kinase Cα (PKCα) in the hippocampus was tested with Western blot analysis. The results showed that the SM level of blood in SMS2(-/-) pups was significantly lower than that in WT pups. No matter in SMS2(-/-) or WT mice, the prenatal alcohol exposure down-regulated the SM levels in pups with dose-dependency. In both SMS2(-/-) and WT pups, the number of proliferative neurons and newborn neurons in the dentate gyrus gradually decreased with the growing age. Compared with the WT pups, SMS2(-/-) pups showed significantly more proliferative neurons and newborn neurons in the dentate gyrus. Notably, prenatal alcohol exposure dose-dependently increased proliferative neurons and newborn neurons in the dentate gyrus in both WT and SMS2(-/-) pups. The hippocampal expression of PKCα protein in SMS2(-/-) mice was lower than that in WT mice, and prenatal alcohol exposure could up-regulate the PKCα protein expression in both WT and SMS2(-/-) mice with dose dependency. These results suggest that alcohol exposure during pregnancy can induce the compensatory neural cell proliferation and the production of newborn neurons in offspring, and the Cer-ceramide-1-phosphate (C1P) pathway is involved in alcohol-induced neural cell proliferation. The activation of PKCα may be a key step to start the Cer-C1P pathway and up-regulate the alcohol-induced neural cell proliferation and the newborn neurons formation.
Animals ; Animals, Newborn ; Cell Proliferation ; drug effects ; Cells, Cultured ; Ceramides ; metabolism ; Dentate Gyrus ; cytology ; Ethanol ; toxicity ; Female ; Mice ; Mice, Knockout ; Neurons ; cytology ; Pregnancy ; Prenatal Exposure Delayed Effects ; physiopathology ; Protein Kinase C-alpha ; metabolism ; Signal Transduction ; Transferases (Other Substituted Phosphate Groups) ; genetics

Aim To explore the effect and mechanism of antioxidant peptide AOP1 on repair of skin burn wound healing in mice.Methods Fluorescence probe DCFH-DA was used to detect the changes of intracellular reactive oxygen species (ROS).Cell proliferation and migration assay were used to detect AOP1 toxicity and its effect on wound healing.Moreover,the skin scald wound was made on the shaved dorsum of the anesthetized mice with a 1.0 cm diameter brass cylinder heated in a water bath at 80 ℃ for 2 min and pressed against the rat skin for 10 s.The effects of AOP1 on the healing of skin burns were observed by HE and Masson staining and the contents of MDA and the activity of SOD in skin tissues were measured.Results The antioxidant peptide AOP1 could significantly reduce the number of ROS in HaCaT and L929 cells,and promote cell migration and proliferation.Compared with the untreated group,the skin healing time of AOP1 group was short,the healing rate was high,the area of scab was small,and inflammation and the content of MDA in burned tissue significantly decreased.The effect of AOP1 on healing of burn wound healing was also confirmed by HE and Masson staining.Conclusion It is suggested that the antioxidant peptide AOP1 with natural activity may promote the healing of skin burns by reducing the oxidative stress caused by burns.

OBJECTIVETo investigate the relationship between EGFR activation and down-regulation of miRNA-145 in lung cancer.

METHODSNormal human lung epithelia cell line (BEAS-2B), human lung adenocarcinoma cell lines with wild-type EGFR (A549 and H292) and human lung adenocarcinoma cell lines with EGFR mutation (H1975 and H1650) were chosen in this study. The levels of miRNA-145 and p-EGFR were determined by quantitative real-time PCR (qRT-PCR) and Western blotting, respectively, and the relationship between p-EGFR and miRNA-145 levels was analyzed. The miRNA-145 levels were determined by qRT-PCR after activating EGFR with EGF or blocking EGFR signal pathway with AG1478. In addition, ERK1/2 inhibitor U0126 was used to inhibit ERK1/2 activation and then the expression of miRNA-145 was detected.

RESULTSThe miRNA-145 levels were closely negatively related with p-EGFR in lung cancer cells (r = -0.926, P = 0.024). EGF down-regulated miRNA-145 expression, particularly in BEAS-2B cells (53.0%; t = 30.993, P = 0.001) and A549 cells (42.6%; t = 14.326, P = 0.005).The miRNA-145 was up-regulated after inhibiting p-EGFR with AG1478, and significantly enhanced by 67.5% in H1975 cells when treated with AG1478 (t = 8.269, P = 0.014). The ERK1/2 signal pathway was activated by p-EGFR. U0126 restored the miRNA-145 down-regulation induced by EGFR-activation in lung cancer cells.

CONCLUSIONThe activation of EGFR down-regulates miRNA-145 expression through ERK1/2 in lung cancer cells.

Butadienes ; pharmacology ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Cell Line ; Cell Line, Tumor ; Down-Regulation ; Enzyme Activation ; drug effects ; Enzyme Inhibitors ; pharmacology ; Epidermal Growth Factor ; pharmacology ; Epithelial Cells ; metabolism ; Humans ; Lung ; cytology ; Lung Neoplasms ; metabolism ; pathology ; MAP Kinase Signaling System ; MicroRNAs ; metabolism ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Nitriles ; pharmacology ; Phosphorylation ; Quinazolines ; pharmacology ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; metabolism ; Tyrphostins ; pharmacology