Objective To develop a diclofenac sodium-loaded gelatin scaffold with anti-inflammatory activity and provide a new avenue for alleviating the inflammatory response and enhancing cartilage regeneration in vivo. Methods Diclofenac sodium was homogeneously mixed with gelatin to prepare a diclofenac sodium-loaded porous gelatin scaffold by freeze-drying method as the experimental group, and a pristine porous gelatin scaffold was served as a control group. The general morphology of the scaffold was observed, the pore size of the scaffold was measured by scanning electron microscopy, the porosity of the scaffold was calculated by drainage method, the loading of diclofenac sodium into the gelatin scaffold was detected by fourier transform infrared spectrometer and X-ray diffraction examinations, and the release kinetics of diclofenac sodium from gelatin scaffold was tested using an in vitro release assay. The two scaffolds were co-cultured with lipopolysaccharide-predisposed RAW264.7 in vitro, and the expressions of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were detected by reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immuno sorbent assay, and Western blot, to detect the in vitro anti-inflammatory effect of the drug-loaded scaffold. Thereafter, the second generation chondrocytes of New Zealand white rabbits were inoculated on the two groups of scaffolds for in vitro culture, and the cytocompatibility of the scaffold was tested by live/dead staining and cell counting kit 8 assay, the feasibility of in vitro cartilage regeneration of the scaffold was evaluated via gross observation, HE staining, Safranin-O staining, and immunohistochemical collagen type Ⅱ staining, as well as biochemical quantitative analyses. Finally, the two groups of chondrocyte-scaffolds were implanted subcutaneously into New Zealand white rabbits, and after 4 weeks, the general observation, HE staining, safranin O staining, immunohistochemical collagen type Ⅱ staining, and biochemical quantitative analyses were performed to verify the cartilage regeneration in vivo, and the expression of inflammation-related genes CD3 and CD68 was detected by RT-PCR to comprehensively evaluate the anti-inflammatory performance of the scaffolds in vivo. Results The two scaffolds exhibited similar gross, microporous structure, pore size, and porosity, showing no significant difference (P>0.05). Diclofenac sodium was successfully loaded into gelatin scaffold. Data from in vitro anti-inflammatory assay suggested that diclofenac sodium-loaded gelatin scaffold showed alleviated gene and protein expressions of IL-1β and TNF-α when compared with gelatin scaffold (P<0.05). The evaluation of cartilage regeneration in vitro showed that the number of living cells increased significantly with the extension of culture time, and there was no significant difference between the two groups at each time point (P>0.05). White cartilage-like tissue was regenerated from the scaffolds in both groups, histological observation showed typical cartilage lacuna structure and specific cartilage extracellular matrix secretion. There was no significant difference in the content of cartilage-specific glycosaminoglycan (GAG) and collagen type Ⅱ between the two groups (P>0.05). In vivo experiments showed that the samples in the experimental group had porcelain white cartilage like morphology, histologic staining showed obvious cartilage lacuna structure and cartilage specific extracellular matrix, the contents of GAG and collagen type Ⅱ were significantly higher than those in the control group, and the protein and mRNA expressions of CD3 and CD68 were significantly lower than those in the control group, with significant differences (P<0.05). ConclusionThe diclofenac sodium-loaded gelatin scaffold presents suitable pore size, porosity, and cytocompatibility, as well as exhibited satisfactory anti-inflammatory ability, providing a reliable scheme for alleviating the inflammatory reaction of regenerated cartilage tissue after in vivo implantation and promoting cartilage regeneration in vivo.
ObjectiveTo establish a more accurately method to detect the residue of 1,4-butanediol diglycidyl-ether (BDDE) in the cross-linked sodium hyaluronic gel so as to provide a scientific testing method for the quality control. MethodsThe gas chromatography was used to explore the thermal stability of BDDE, and the residues of BDDE in sodium hyaluronic gel was detected by fluorescence spectrophotometry. The hyaluronidase was added to the BDDE standard solution and the improved fluorescence spectrophotometer was used to detect the BDDE residues in the cross-linked hyaluronic sodium gel. ResultsA good linearity was obtained as y=14.102x+1.103 (R2=0.999 8) for BDDE. BDDE was unstable under high temperature and long storage time. The relevant fluorescence intensity was detected with hyaluronidase solution. After adding hyaluronidase into the BDDE standard solutions, the advanced linearity was obtained as y=14.027x+7.062 (R2=0.999 9). ConclusionFluorescent spectrophotometry is a simple, rapid, and accurate method to analyze BDDE residue of cross-linked sodium hyaluronic gel. Due to the poor thermal stability, all the factors related to temperature must be excluded during the process, including the temperature control of every step. Furthermore, the adding of hyaluronidase in the pre-preparation of cross-linked sodium hyaluronic gel can bring interference. So when using fluorescent spectrophotometry, adjustment must be taken before the calibration curve is preparation.
Objective To study the clinical efficacy of topiramate combined with carbamazepine combined with phenytoin in elderly seizures. Methods A total of 105 elderly patients with epilepsy were enrolled in this study from August 2014 to July 2016 in Fuzhou Chinese and Western Medicine Hospital. The patients were aged 61 to 80 years. There were 42 males and 63 females with epilepsy. The course were 1 to 5 years; 55 cases were partial onset, 50 cases were systemic attack. According to the different treatment methods, the patients were divided into A, B, C three groups, each group were 35 patients. Group A was daily treated with 4 to 8 mg/kg topiramate; Group B was treated with 0.3 g carbamazepine combined with 250 to 300 mg phenytoin per day. Group C was daily treated with 4 to 8 mg/kg topiramate and 0.3 g carbamazepine combined with 250 to 300 mg phenytoin. The total effective rate, the incidence of adverse reactions, the number of seizures before and after treatment were compared among the three groups. Results The total effective rate of group C was higher than that of group A and B, and the difference was statistically significant (P<0.05). There were no significant differences in the number of epileptic seizures between the three groups before treatment (P>0.05). The number of seizures in group C was significantly lower than that in group A and B (P<0.05). Conclusions The treatment of topical epilepsy patients with topiramate and carbamazepine combined with phenytoin can significantly improve the total effective rate of treatment, protect the safety of medication, reduce the number of patients with epilepsy, so that patients can quickly return to normal life. It would be worthy for clinical promotion and use.
Objective To evaluate the effectiveness and safety of foscarnet sodium in the treatment of chronic hepatitis B. Methods We searched MEDLINE, EMbase, The Cochrane Library and CNKI from 1978 to June 2006. Randomized controlled trials of foscarnet sodium versus other drugs or no drugs in the treatment of chronic hepatitis B were identified. The quality of the included trials was evaluated by two reviewers independently. Meta-analysis was done using The Cochrane Collaboration’s RevMan 4.2.7. Results Seven studies (337 patients) were included; one compared foscarnet sodium versus interferon, and the other six compared foscarnet sodium versus no drugs. All the included studies were graded in terms of the quality of randomization, allocation concealment and blinding. All 7 studies were graded as level C. The meta-analysis showed that: ① foscarnet sodium was not significantly different from interferon in clinical efficacy, liver function, negative-conversion rate of virological markers and side effects. ② compared with the no drugs group, the negative-conversion rate of virological markers was significantly higher for the foscarnet sodium group, HBeAg (RR 6.20, 95%CI 1.76 to 21.79) and HBV-DNA (RR 4.13, 95%CI 1.32 to 12.86); but there were no significant differences in clinical efficacy, liver function and side effects. Conclusions Available evidence shows that: in the treatment of chronic hepatitis B the effectiveness and safety of foscarnet sodium are not significantly different from interferon, but only one trial is included in this review, so the evidence is weak. Compared with no drugs, foscarnet sodium significantly improves the negative-conversion rate of virological markers, but the evidence is insufficient to show whether foscarnet sodium could improve clinical efficacy and liver function, as well as reduce side effects.
The effects on rat’s liver preservation using HX solation with high potassium and low sodium or HXm solution with high sodium and low potassium were studied with isolated perfusion of rat livers (IPRL). Sixty inbred Wistar rats were randomly divided into group HX (preserved with HX solution, n=30) and group HXm (preserved with HXm solution,n=30). The preservation effects of the storage solutions were assessed by measuring the sinunoidal lining cell mortality (SLCM), the Krebs-hense-leit perfusate ketone bidy ratio (PKBR), the hepatic sugar release (SL), and the hepatic tissue water content (HTWC). The results showed that there no significant differences between the two storage solutions after 6 hours preservation. If the preserved time was prolonged to 12 hours or more, the effect of rat’s liver preservation using HX solution were much superior to those using HXmsolutin.
ObjectiveTo systematically review the diagnostic value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for liver metastases. MethodsWe searched databases including CNKI, CBM, VIP, WanFang Data, PubMed, EMbase and The Cochrane Library from January 2011 to December 2014 to collect diagnostic tests about Gd-EOB-DTPA for liver metastases. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies by using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) tool. Then, meta-analysis was performed by using Stata 12.0 software. ResultsA total of 15 studies from seven countries were included, involving 2 040 nodules from 701 patients. The results of meta-analysis showed that, the pooled sensitivity (Sen), specificity (Spe), positive likelihood ratio (+LR), negative likelihood ratio (-LR) and diagnostic odds ratio (DOR) of Gd-EOB-DTPA for liver metastases were 0.92 (95%CI 0.89 to 0.95), 0.94 (95%CI 0.89 to 0.97), 14.51 (95%CI 8.01 to 26.28), 0.08 (95%CI 0.06 to 0.12), and 177.98 (95%CI 89.50 to 353.94), respectively. The area under curve (AUC) of SROC was 0.97 (95%CI 0.95 to 0.98). The results of subgroup analysis showed that Gd-EOB-DTPA had better Sen in nodules >10 mm than the nodules ≤10 mm in diameter (>10 mm: pooled Sen=0.97, 95%CI 0.94 to 0.99; ≤10 mm: pooled Sen=0.75, 95%CI 0.65 to 0.85; P<0.001); The 3.0T MR had better Sen in diagnosing liver metastases compared with 1.5T MR (3.0T: pooled Sen=0.95, 95%CI 0.92 to 0.97; 1.5T: pooled Sen=0.90, 95%CI 0.87 to 0.94; P<0.001). ConclusionGdEOB-DTPA is of value for the detection of liver metastases. In particular, it is of high sensitivity for the detection of nodules larger than 10 mm, and for the cases using 3.0T high-field MR system. Due to limited quantity and quality of the included studies, more high-quality studies are required to verify the above conclusion.
Objective To investigate the retinal toxicity and verify the safe dose of intravitreal injection of nonsteroid anti-inflamatory drug,diclofenac sodium.Methods Twenty-eight healthy adult white rabbits were divided at random into 7 groups and received in every right eye the intravitreal injection of a single dose of diclofenac sodium solution ranging from 0.4-0.1 mg/0.1ml respectively ,the left eyes were regarded as conreol ones.Before injection and on the 1st,3rd,7th,14th,21st,and 28th day after injection the electroretinography on both eyes was examined.On the 28th day after injection the retinas of two rabbits of every group were examined by using light microscopy.On the 10th and 30th day after injection the retinal tissues around the optic nerve sisk of two eyes from every group at random were tested by using transmission electron microscopy.Results The retio of amplitude ofb wave of electroretinography in 0.4mg and 0.5mg groups had no sighnificant difference from groups before injection,the retinal tissues showed no structural changes in light and ecectron microscopy examination.The ratio of amplitude ofb wave of photoptic electroretinogrphy in 0.6mg groups in the early stage after injection was markedly reduced（P＜0.05）and returned to that before injection with time,reversible change of the edematou retina was discovered.The ratio of amplitude of b wave of electroretinography in 0.7-1.0mg groups was distinctly descreaded after injection（P＜0.05 or P＜0.01）,the cells of all the retinal layer revealed apparent and irreversible damage.Conclusion The largest dose of safety of intravitreal diclofenac sodium should be not more than 0.6mg.The toxic effect of intravitreal diclofenac sodium on retina is concerned mostly to cones and rods.
Objective To analyze the clinical application, ADR/AE involved systems and manifestations of the six injections containing Houttuynia cordata which are much complicated in their ingredients and pharmacological actions compared with the Houttuynia cordata Injection, and to assess their safety and efficacy, so as to provide references for further deep research. Methods Such databases as MEDLINE (1998 to December 31, 2010), EMBASE (1998 to December 31, 2010), The Cochrane Library (1998 to December 31, 2010), CNKI (1979 to December 31, 2010), CBM (1978 to December 31, 2010), and VIP (1989 to December 31, 2010) were searched to retrieve the case report, series of cases observation, cross-sectional study, and clinical control study. The studies were included according to the inclusive and exclusive criteria, and the data was abstracted to analyze the reason and regularity of ADR/AE. Meta-analyses for efficacy were conducted when the data was feasible. Results a) About ADR/AE: Among the included 132 studies, 118 cases were reported with the ADR/AE. There were 59 studies about the New Houttuyfonate sodium injection, 93 cases with ADR/AE mainly manifested as pain in injection site (41 cases), rash (19 cases), anaphylactic shock (11 cases) and other infusion or allergic reactions (21 cases). There were 69 studies about the Yu Jin injection, 25 cases with ADR/AE manifested as rash (12 cases), anaphylactic shock (four cases), pain in injection site (three cases), and other infusion or allergic reactions (six cases); and b) The good efficacy of the New Houttuyfonate sodium injection and the Yu Jin injection was reported in one cross-sectional study and one RCT respectively, but the limited data was not enough to properly judge the efficacy. Conclusion There are few of clinical studies about these six injections containing Houttuynia cordata, and the irrational use in clinic is serious. Most of the ADR/AE cases are related to irrational use, such as, non-indication use, and arbitrarily change of administration method. The proof for analyzing and evaluating the safety and efficacy of injections containing Houtturnia cordata is insufficient, so strict clinical trials with large sample size are required to support further research.
ObjectiveTo systematically evaluate the efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS) versus mycophenolate mofetil (MMF) in kidney transplant recipients. MethodsWe searched MEDLINE, EMbase, PubMed, the Cochrane Library (Issue 9, 2013), CBM, CNKI, VIP and WanFang Data from their inception to November 2013, to collect randomized controlled trials (RCTs) of EC-MPS versus MMF in kidney transplant recipients. References of included studies were also retrieved. Two reviewers independently screened studies according to the exclusion and inclusion criteria, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.1 software. ResultsA total of 8 RCTs involving 2 400 patients were included. The results of meta-analysis indicated that there were no significant differences between the two groups at the end of 4-week, 6-month, 12-month and 48-month follow-up in the acute rejection rate (4-weeks:RR=0.33, 95%CI 0.01 to 8.05; 6 months:RR=0.94, 95%CI 0.73 to 1.22; 12 months:RR=0.88, 95%CI 0.63 to 1.24; 4 years:RR=0.93, 95%CI 0.47 to 1.84). There were no significant differences between the two groups at the end of 6-month and 12-month follow-up in the chronic rejection rate (6 month:RR=0.66, 95%CI 0.27 to 1.58; 12 month:RR=0.57, 95%CI 0.29 to 1.15). There were no significant differences between the two groups at the end of 6-month, 12-month and 48-month follow-up in the graft loss or death rate (6-month:RR=0.79, 95%CI 0.41 to 1.50; 12-month:RR=0.76, 95%CI 0.40 to 1.43; 48-month:RR=1.38, 95%CI 0.59 to 3.23). As to the side effect, EC-MPS could significantly reduce the risk of pneumonia compared with MMF (RR=0.32, 95%CI 0.13 to 0.79). ConclusionBased on current evidences, EC-MPS is comparable with MMF for renal transplant patients in short-term effectiveness, and the incidence of pneumonia in the EC-MPS group is lower than the MMF group. Due to the limited quantity and quality of the studies, the conclusions should be validated by more high quality studies.
ObjectiveTo evaluate the preemptive analgesic efficiency of parecoxib on patients undergoing inguinal hernia repair. MethodsOne hundred and twenty patients scheduled for surgery between May and August 2013 were randomized into group A (n=60) and group B (n=60). Patients in group A received intravenous parecoxib sodium (40 mg) for 45 minutes before surgery while group B received equivalent normal saline. All patients underwent tension-free hernia repair under local anesthesia with simplex lidocaine. Visual analogy scores (VAS) after surgery and the maximum VAS were recorded. The number of patients requiring rescue analgesic (tramadol injection) or with adverse effects related to analgesia were observed and recorded. Postoperative hospital stay and patient satisfaction score with analgesic effect were compared between the two groups. Concentrations of plasma prostaglandin E2(PGE2) before surgery and 24 hours after surgery were measured in both groups. ResultsVAS scores were significantly lower in group A at 2, 4, 8 and 12 hours after surgery than group B, while no significant difference was seen after 24 hours of the surgery. The number of patients requiring tramadol (3/60) or with adverse effects (2/60) in group A were significantly lower than that in group B (11/60 and 8/60 respectively). Postoperative hospital stay was shorter while patient satisfaction score with analgesic effect was higher in group A than in group B. There were no significant differences in concentration of plasma PGE2 between the two groups before surgery and after 24 hours of the surgery (P>0.05). ConclusionPreemptive administration of parecoxib for hernia repair can result in significant analgesic effect with fewer adverse effects, higher patient satisfaction and faster recovery.