Objective To prepare a novel hyaluronic acid methacrylate (HAMA) hydrogel microspheres loaded polyhedral oligomeric silsesquioxane-diclofenac sodium (POSS-DS) patricles, then investigate its physicochemical characteristics and in vitro and in vivo biological properties. Methods Using sulfhydryl POSS (POSS-SH) as a nano-construction platform, polyethylene glycol and DS were chemically linked through the “click chemistry” method to construct functional nanoparticle POSS-DS. The composition was analyzed by nuclear magnetic resonance spectroscopy and the morphology was characterized by transmission electron microscopy. In order to achieve drug sustained release, POSS-DS was encapsulated in HAMA, and hybrid hydrogel microspheres were prepared by microfluidic technology, namely HAMA@POSS-DS. The morphology of the hybrid hydrogel microspheres was characterized by optical microscope and scanning electron microscope. The in vitro degradation and drug release efficiency were observed. Cell counting kit 8 (CCK-8) and live/dead staining were used to detect the effect on chondrocyte proliferation. Moreover, a chondrocyte inflammation model was constructed and cultured with HAMA@POSS-DS. The relevant inflammatory indicators, including collagen type Ⅱ, aggrecan (AGG), matrix metalloproteinase 13 (MMP-13), recombinant A disintegrin and metalloproteinase with thrombospondin 5 (Adamts5), and recombinant tachykinin precursor 1 (TAC1) were detected by immunofluorescence staining and real-time fluorescence quantitative PCR, with normal cultured chondrocytes and the chondrocyte inflammation model without treatment as control group and blank group respectively to further evaluate their anti-inflammatory activity. Finally, by constructing a rat model of knee osteoarthritis, the effectiveness of HAMA@POSS-DS on osteoarthritis was evaluated by X-ray film and Micro-CT examination. Results The overall particle size of POSS-DS nanoparticles was uniform with a diameter of about 100 nm. HAMA@POSS-DS hydrogel microspheres were opaque spheres with a diameter of about 100 μm and a spherical porous structure. The degradation period was 9 weeks, during which the loaded POSS-DS nanoparticles were slowly released. CCK-8 and live/dead staining showed no obvious cytotoxicity at HAMA@POSS-DS, and POSS-DS released by HAMA@POSS-DS significantly promoted cell proliferation (P<0.05). In the chondrocyte anti-inflammatory experiment, the relative expression of collagen type Ⅱ mRNA in HAMA@POSS-DS group was significantly higher than that in control group and blank group (P<0.05). The relative expression level of AGG mRNA was significantly higher than that of blank group (P<0.05). The relative expressions of MMP-13, Adamts5, and TAC1 mRNA in HAMA@POSS-DS group were significantly lower than those in blank group (P<0.05). In vivo experiments showed that the joint space width decreased after operation in rats with osteoarthritis, but HAMA@POSS-DS delayed the process of joint space narrowing and significantly improved the periarticular osteophytosis (P<0.05). Conclusion HAMA@POSS-DS can effectively regulate the local inflammatory microenvironment and significantly promote chondrocyte proliferation, which is conducive to promoting cartilage regeneration and repair in osteoarthritis.
ObjectiveTo observe the efficacy and safety of etofenamate gel (foscavir+tramadoli hydrochloridum+gabapentin) in the treatment of acute herpes zoster. MethodsForty patients with acute herpes zoster neuralgia treated between January 2013 and June 2014 were randomly divided into two groups:control group and treatment group, with 20 in each. The patients had a visual analogue scale (VAS) pain score of seven or higher. Patients in the control group accepted conventional treatment, while those in the treatment group were treated with conventional treatment combined with etofenamate gel. Two weeks after treatment, VAS score, quality of life and sleep score, and the degree of improvement in skin paresthesia were evaluated and compared between the two groups. ResultsThe VAS score decreased significantly in both the two groups after treatment (P < 0.05), and the decrease in the treatment group was significantly more obvious (P < 0.05). The quality of life, sleep score and the degree of improvement in skin paresthesia were ameliorated significantly after treatment (P < 0.05), and the amelioration in the treatment group was significantly greater (P < 0.05). ConclusionThe early application of Ordofen can strengthen analgesia effect of the conventional treatment, improve the quality of life and sleep, and reduce skin paresthesia.
目的 探讨单用和联用盐酸氨基葡萄糖与非甾体抗炎药（NSAID）在椎间盘源性腰痛（DLBP）治疗中的有效性。 方法 2011年1月－12月72例DLBP患者，男42例，女30例；年龄22～71岁；体重43～84 kg；病程0.5～10年。通过随机数字表的方法，将患者分为3组。A组给予盐酸氨基葡萄糖胶囊750 mg，2次/d，同时给予尼美舒利分散片100 mg，2次/d；B组给予盐酸氨基葡萄糖胶囊750 mg，2次/d；C组给予尼美舒利分散片100 mg，2次/d。3组均用药8周后停药，用药期间停用其他活血化瘀类药物及物理治疗。选取治疗前及治疗后第4、8、16周4个时间点，运用疼痛数字评价量表（NRS）、Oswestry功能障碍指数（ODI）、生活质量评价量表SF-36分别对3组患者的腰痛、腰部功能及生活质量进行评价。 结果 63例获得随访，失访率12.5%。各组患者NRS评分、ODI评分、SF-36评分在治疗前后比较差异均有统计学意义（P＜0.05），A组疗效明显优于B、C两组，B组治疗后各项数据较治疗前明显改善（P＜0.05）。 结论 单用盐酸氨基葡萄糖治疗DLBP有效，且在停药后，仍有一定疗效，联用NSAID效果更佳；远期疗效有待进一步随访。
ObjectiveTo study the potential protective effects of bone marrow mesenchymal stem cells (BMSCs) on chondrocytes injured by interleukin 1β (IL-1β), and the resistant capacity of chondrocytes when co-cultured indirectly with BMSCs against IL-1β. MethodsSix Sprague Dawley (SD) rats were randomly divided into experimental group (articular cartilage defects) and control group. The content and gene expression of IL-1β were detected at 6 hours after surgical intervention by quantitative real time RCR (qRT-PCR) and ELISA. BMSCs repairing function test: the 18-holes cultured chondrocytes were randomly divided into 3 groups (n=6): cells of blank group were not treated;cells of injured group and co-cultured group were intervened by IL-1β, and Transwell chamber was used to establish co-culture system of BMSCs with chondrocyte in co-cultured group. The mRNA relative expressions of cysteinyl aspartate specific proteinase 3 (Caspase 3), a disintegrin and metalloprotease with Thrombospondin motifs 4 (ADAMTS-4), and ADAMTS-5 were measured via qRT-PCR in chondrocytes, meanwhile Caspase-3 content was detected via ELISA, and the cell apoptosis rate was detected via flow cytometry. BMSCs protecting function test: the 12-holes cultured chondrocytes were randomly divided into 2 groups (n=6), Transwell chamber was used to establish co-culture system of BMSCs with chondrocyte in co-cultured group before the 2 groups were both intervened by IL-1β, then the same detected indexes were taken as the BMSCs repairing function test. ResultsAnimal in vivo studies showed that relative expression of IL-1β mRNA and IL-1β contents were significantly higher in experimental group than control group (P<0.05). BMSCs repair tests showed that mRNA relative expressions of Caspase-3, ADAMTS-4, and ADAMTS-5, Caspase-3 content, and cell apoptosis rate were significantly higher in injured group and co-cultured group than blank group, and in injured group than co-cultured group (P<0.05). BMSCs protect tests showed that mRNA relative expressions of Caspase-3, ADAMTS-4, and ADAMTS-5, Caspase-3 content, and cell apoptosis rate in co-cultured group were significantly lower than those in control group (P<0.05). ConclusionBMSCs, as seed cells for tissue engineering, have potential for applications to anti-inflammation and anti-apoptosis.
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.
ObjectivesTo systematically review the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) on tennis elbow.MethodsPubMed, EMbase, The Cochrane Library, VIP, CNKI and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) on NSAIDs for tennis elbow from inception to May 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 8 RCTs involving 595 patients were included. The results of meta-analysis showed that there were no significant differences in the therapeutic effect between NSAIDs and the placebo group (RR=1.10, 95%CI 0.89 to 1.35, P=0.39) or non-placebo control group (RR=0.88, 95%CI 0.77 to 1.00, P=0.06). Compared with non-placebo control group, NSAIDs group had lower VAS score difference (MD=−1.41, 95%CI −2.28 to −0.53, P=0.002).ConclusionsCurrent evidence shows that the effect of NSAIDs on tennis elbow is still uncertain. The improvement of symptoms with NSAIDs may be superior to placebo, but inferior to other treatment methods. Due to the limited quantity and quality of included studies, the above conclusions are required to be verified by more high-quality studies.
Objective To improve the knowledge of epidemiology, diagnosis and treatment of aspirin induced asthma ( AIA) in China. Methods Thirty-six cases with AIA who were reported in 30 papers in recent 10 years were analyzed retrospectively. Results The drugs which induced AIA in China mainly included acetylsalicylic acid ( aspirin) , ibuprofen ( Fenbid, ibuprofen) , while acetaminophen ( paracetamol,Bufferin, Tylenol ) , phenylpropanoid thiazide ( Piroxicam) , methoxy-naphthalene C acid ( naproxen) ,diclofenac in rare cases. 28. 6% ( 8 /28) of AIA patients were complicated with nasal disease . AIA could occur at all ages, especially for those over 40 years ( 72. 2% , 26 /36) . No significant difference of prevalencein male and female. The onset time of AIA was less than 60min in 71. 4% and gt;120min in 38. 6% . Most patients took the medications by oral ( 83. 3% ,30/36) , but the AIA onset time was not different by different administration route. Conclusions The incidence of AIA increases in recent years because of widely use of NSAIDs. However, no awareness of NSAIDs induced asthma is common in patients and physicians. For asthma patients it must be caution to take antipyretic analgesic anti-inflammatory drugs. If necessary,methoxy-naphthalene C acid ( naproxen) and diclofenac could be better choice.
ObjectivesTo systematically review the risk factors for intestinal injury induced by non-steroidal anti-inflammatory drugs(NSAIDs).MethodsWe comprehensively searched WanFang Data, CNKI, Web of Science, EBSCO, PubMed and The Cochrane Library databases to collect studies on risk factors of NSAIDs-induced intestinal injury. Two reviewers independently screened literature, extracted data and assessed risk of bias, and then, meta-analysis was performed by using RevMan 5.2 and STATA 12.0 software.ResultsA total of 6 case-control studies were included, in which 265 patients were in the case group and 301 patients in the control group. The results of meta-analysis showed that PPI was an independent risk factor for NSAIDs-induced intestinal injury (OR=1.59, 95%CI 1.07 to 2.35, P=0.02). In addition, patients with osteoarthritis (OR=2.44, 95% CI 1.11 to 5.36, P=0.03) or rheumatoid arthritis (OR=3.04, 95% CI 1.31 to 7.03, P=0.01) was associated with intestinal mucosal injury induced by NSAIDs. Gender, age, smoking history, drinking history, H2RA and rebamipide medication history, cardiovascular disease and cerebrovascular disease were not associated with intestinal injury.ConclusionsPPI is an independent risk factor for NSAIDs-induced intestinal injury. However, studies with high-quality, larger sample size are required to further verify that PPI increases the prevalence of intestinal injury.
Objective To observe the therapeutic effect of thermosensitive hydrogel containing curcumin-vitamin E (VE) complex (hereinafter referred to as “curcumin-VE hydrogel”) on radiation-induced oral mucositis in mice. Methods Curcumin-VE hydrogel was prepared using the synthesized curcumin-VE complex as the carrier and poloxam as the substrate. The structure of curcumin-VE complex was characterized by Fourier transform infrared spectrometer, the microstructure of curcumin-VE hydrogel was determined by scanning electron microscope, and the gelation temperature was determined by rheometer, gel swelling and degradation were tested and gel adhesion was determined using a universal testing machine. Thirty healthy male BALB/C mice with specific pathogen free grade were randomly divided into three groups, with ten mice in each group. The radiation group and radiation+hydrogel group were modeled by a single high dose of radiation (25 Gy), while the control group had anesthesia but no radiation. The control group and radiation group were given daily feed and water 7 days after radiation. In addition to daily feed and water, the radiation+hydrogel group was given curcumin-VE hydrogel twice a day. The mice were sacreficed on the 8th day after radiation. The weight changes of each group were recorded after radiation. The ulceration area of tongue was measured by toluidine blue. The tongue of mouse were pathologically observed. The activities of superoxide dismutase, catalase (CAT), and glutathione peroxidase and the level of malondialdehyde in tongue tissue were determined. The levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in tongue tissue were determined by enzyme linked immunosorbent assay. The distribution and positive expression of phosphorylated histone H2AX (γ-H2AX) and nuclear factor-erythroid 2-related factor 2 were determined by immunohistochemistry. Results Curcumin-VE hydrogel had a porous network structure and the gelation temperature was 30℃, the swelling rate was close to 300%, the gel degradation rate was up to 95% after 48 h, and the adhesion strength was 12.748 kPa. Compared with the radiation group, the weight of mice in the radiation+hydrogel group increased (P<0.05), the ulcer area decreased (P<0.05); the activity of CAT increased (P<0.05); the levels of TNF-α, IL-1β and IL-6 decreased (P<0.05); the expression of γ-H2AX was down-regulated (P<0.05). Conclusion Curcumin-VE hydrogel can delay or weaken the process of radiation-induced oral mucositis by reducing the DNA damage caused by radiation, inhibiting the production of reactive oxygen species, and effectively reducing the level of inflammation in tongue tissue.