The effectiveness and safety of Tripterygium wilfordii glycosides combined with disease-modifying anti-rheumatic drugs in the treatment of rheumatoid arthritis: A systematic review and meta-analysis of 40 randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis were performed to investigate the efficacy and safety of Tripterygium wilfordii glycosides (TG) for rheumatoid arthritis (RA) from the current literature. METHODS: An electronic search was conducted in eight databases (PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese VIP Database, and Wanfang Database) from inception until September 2020. Randomized controlled trials (RCTs) with risk of bias (RoB) score ≥ 4 according to the Cochrane RoB tool were included for the analyses. The primary outcome measures were duration of morning stiffness (DMS), tender joint count (TJC), swollen joint count (SJC), visual analog score (VAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF). The secondary outcome measures were the total clinical effective rate and adverse events. All the analyses were used by the random effects models. The meta-analysis was performed using RevMan 5.3 and STATA 14.0. RESULTS: A total of 40 RCTs with 3092 patients met our inclusion criteria. This meta-analysis showed that TG plus DMARDs for RA could decrease the DMS (p < .001), TJC (p < .001), SJC (p < .001), VAS (p < .001), serum CRP (p < .001), ESR (p < .001), and RF (p < .001) and improve total effective rate (p < .001). In addition, TG was generally safe and well tolerated in RA patients. CONCLUSION: Despite the limitations, the present evidence supports, at least to an extent, that TG can be recommended for routine use for RA patients. More large multicenter and high-quality RCTs are required for further research.

An injectable liposome for sustained release of tanshinone IIA to the treatment of acute blunt muscle injury by augmenting autophagy and alleviating oxidative stress.

Acute blunt skeletal muscle injury occurs frequently in sports and traffic accidents, and even leads to muscle necrosis and impaired functionality. Current treatment options for muscle injuries remain suboptimal and often result in delayed/incomplete recovery of damaged muscles. Tanshinone IIA is extracted from Salvia Miltiorrhizae, which is effective in the treatment of injury repair. But the clinical application of tanshinone IIA is limited due to its low water solubility, low permeability to biofilm and low bioavailability. In this study, tanshinone IIA liposomes were prepared to improve the bioavailability and sustained release of tanshinone IIA. The particle size, dispersion coefficient, zeta potential, encapsulation efficiency (EE) and drug loading (DL) of tanshinone IIA liposomes were 150.67 ± 27.23 nm, 0.20 ± 0.015, -8.73 ± 2.28 mV, 70.32 ± 4.04% and 15.63%, respectively. The results of quantitative real-time polymerase chain reaction (QRT-PCR) showed that tanshinone IIA liposome significantly promoted the expression of vimentin and reduce MHCIIB expression compared with other groups (P < 0.05). Western blotting showed that tanshinone IIA liposome could effectively promote the expression of autophagy-related proteins (VPS34, Beclin 1 and CTSD) and decrease p62 expression levels to treat injured muscle. Through HE, immunohistochemistry, ELISA and serological tests, we found that tanshinone IIA liposome not only effectively promoted the expression of desmin, but also reduced the expression of collagen-I and inhibited the production of pro-inflammatory factors, such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) (P < 0.05). In addition, tanshinone IIA liposome therapy significantly reduced the level of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD) after muscle injury compared with other groups (P < 0.05). In conclusion, tanshinone IIA liposome possesses an effective therapeutic effect on acute blunt muscle injury in rats by augmenting autophagy and alleviating oxidative stress. The continuous release of tanshinone IIA encapsulated by liposomes for disease treatment provide a new idea for the efficient and safe use of drugs with low lipid solubility and bioavailability for the treatment of acute blunt muscle injury and repair of other injuries.

Paeoniflorin promotes angiogenesis and tissue regeneration in a full-thickness cutaneous wound model through the PI3K/AKT pathway.

The treatment of wounds remains a clinical challenge because of poor angiogenesis under the wound bed, and increasingly, the patients' need for functional and aesthetically pleasing scars. For the wound healing process, new blood vessels which can deliver nutrients and oxygen to the wound area are necessary. In this study, we investigated the pro-angiogenesis ability and mechanism in wound healing of paeoniflorin (PF), which is a traditional Chinese medicine. In our in vitro results, the ability for proliferation, migration and in vitro angiogenesis in human umbilical vein endothelial cells was promoted by coculturing with PF (1.25-5 µM). Meanwhile, molecular docking studies revealed that PF has excellent binding abilities to phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT), and consistent with our western blot results, that PF suppressed PI3K and AKT phosphorylation. Furthermore, to investigate the healing effect of PF in vivo, we constructed a full-thickness cutaneous wound model in rats. PF stimulated the cellular proliferation status, collagen matrix deposition and remodeling processes in vitro and new blood vessel formation at the wound bed resulting in efficient wound healing after intragastric administration of 10 mg·kg-1 ·day-1 in vivo. Overall, PF performed the pro-angiogenetic effect in vitro and accelerating wound healing in vivo. In summary, the capacity for angiogenesis in endothelial cells could be enhanced by PF treatment via the PI3K/AKT pathway in vitro and could accelerate the wound healing process in vivo through collagen deposition and angiogenesis in regenerated tissue. This study provides evidence that application of PF represents a novel therapeutic approach for the treatment of cutaneous wounds.

An injectable thermosensitive hydrogel for sustained release of apelin-13 to enhance flap survival in rat random skin flap.

With the advantage of handy process, random pattern skin flaps are generally applied in limb reconstruction and wound repair. Apelin-13 is a discovered endogenous peptide, that has been shown to have potent multiple biological functions. Recently, thermosensitive gel-forming systems have gained increasing attention as wound dressings due to their advantages. In the present study, an apelin-13-loaded chitosan (CH)/ß-sodium glycerophosphate (ß-GP) hydrogel was developed for promoting random skin flap survival. Random skin flaps were created in 60 rats after which the animals were categorized to a control hydrogel group and an apelin-13 hydrogel group. The water content of the flap as well as the survival area were then measured 7 days post-surgery. Hematoxylin and eosin staining was used to evaluate the flap angiogenesis. Cell differentiation 34 (CD34) and vascular endothelial growth factor (VEGF) levels were detected by immunohistochemistry and Western blotting. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were assessed by enzyme linked immunosorbent assays (ELISAs). Oxidative stress was estimated via the activity of tissue malondialdehyde (MDA) and superoxide dismutase (SOD). Our results showed that CH/ß-GP/apelin-13 hydrogel could not only reduce the tissue edema, but also improve the survival area of flap. CH/ß-GP/apelin-13 hydrogel also upregulated levels of VEGF protein and increased mean vessel densities. Furthermore, CH/ß-GP/apelin-13 hydrogel was shown to significantly inhibit the expression of TNF-α and IL-6, along with increasing the activity of SOD and suppressing the MDA content. Taken together, these results indicate that this CH/ß-GP/apelin-13 hydrogel may be a potential therapeutic way for random pattern skin flap.

Baicalin suppresses IL-1ß-induced expression of inflammatory cytokines via blocking NF-κB in human osteoarthritis chondrocytes and shows protective effect in mice osteoarthritis models.

Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. Baicalin, a predominant flavonoid isolated from the dry root of Scutellaria baicalensis Georgi, has been reported to have anti-inflammatory effects. However, the anti-inflammatory effects of baicalin on OA have not been reported. Our study aimed to investigate the effect of baicalin on OA both in vitro and in vivo. In vitro, human OA chondrocytes were pretreated with baicalin (10, 50, 100µM) for 2h and subsequently stimulated with IL-1ß for 24h. Production of NO and PGE2 were evaluated by the Griess reaction and ELISAs. The mRNA expression of COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5, aggrecan and collagen-II were measured by real-time PCR. The protein expression of COX-2, iNOS, MMP-3, MMP-13, ADAMTS-5, p65, p-p65, IκBα and p-IκBα was detected by Western blot. The protein expression of collagen-II was evaluated by immunofluorescence. Luciferase activity assay was used to assess the relative activity of NF-kB. In vivo, the severity of OA was determined by histological analysis. We found that baicalin significantly inhibited the IL-1ß-induced production of NO and PGE2, expression of COX-2, iNOS, MMP-3, MMP-13 and ADAMTS-5 and degradation of aggrecan and collagen-II. Furthermore, baicalin dramatically suppressed IL-1ß-stimulated NF-κB activation. In vivo, treatment of baicalin not only prevented the destruction of cartilage but also relieved synovitis in mice OA models. Taken together, these results suggest that baicalin may be a potential agent in the treatment of OA.

Effect of Electroacupuncture at The Zusanli Point (Stomach-36) on Dorsal Random Pattern Skin Flap Survival in a Rat Model.

BACKGROUND: Random skin flaps are commonly used for wound repair and reconstruction. Electroacupuncture at The Zusanli point could enhance microcirculation and blood perfusion in random skin flaps. OBJECTIVE: To determine whether electroacupuncture at The Zusanli point can improve the survival of random skin flaps in a rat model. MATERIALS AND METHODS: Thirty-six male Sprague Dawley rats were randomly divided into 3 groups: control group (no electroacupuncture), Group A (electroacupuncture at a nonacupoint near The Zusanli point), and Group B (electroacupuncture at The Zusanli point). McFarlane flaps were established. On postoperative Day 2, malondialdehyde (MDA) and superoxide dismutase were detected. The flap survival rate was evaluated, inflammation was examined in hematoxylin and eosin-stained slices, and the expression of vascular endothelial growth factor (VEGF) was measured immunohistochemically on Day 7. RESULTS: The mean survival area of the flaps in Group B was significantly larger than that in the control group and Group A. Superoxide dismutase activity and VEGF expression level were significantly higher in Group B than those in the control group and Group A, whereas MDA and inflammation levels in Group B were significantly lower than those in the other 2 groups. CONCLUSION: Electroacupuncture at The Zusanli point can effectively improve the random flap survival.

The protective effects of silibinin in the treatment of streptozotocin-induced diabetic osteoporosis in rats.

Diabetic osteoporosis (DO) is a complication of diabetes mellitus. Our previous study showed that silibinin can attenuate high glucose mediated human bone marrow stem cells dysfunction through antioxidant effect. However, no study has yet investigated the effect of silibinin in diabetic rats. Therefore, we assessed the effects of silibinin on bone characteristics in streptozotocin-induced diabetic rats. The aim of our study was to determine whether providing silibinin in the different supplementation could prevent bone loss in diabetic rats or not. Rats were randomly divided into four groups: (1) control group (CG) (n=10); (2) diabetic group (DG) (n=10); (3) diabetic group with 50mgkg-1day-1 of silibinin orally (DG-50) (n=10); and (4) diabetic group with 100mgkg-1day-1 of silibinin orally (DG-100) (n=10). 12 weeks after streptozotocin (STZ) injection, the femora from all rats were assessed and oxidative stress was evaluated. Bone mineral density was significantly decreased in diabetic rats; these effects were prevented by treatment with silibinin (100mgkg-1day-1 orally). Similarly, in the DG and DG-50 groups, changes in microarchitecture of femoral metaphysis assessed by microcomputed tomography demonstrated simultaneous existence of diabetic osteoporosis; these impairments were prevented by silibinin (100mgkg-1day-1 orally). In conclusion, silibinin supplementation may have potential use as a possible therapy for maintaining skeletal health and these results can enhance the understanding of diabetic osteoporosis induced by diabetes.

Comparison of percutaneous cannulated screw fixation and calcium sulfate cement grafting versus minimally invasive sinus tarsi approach and plate fixation for displaced intra-articular calcaneal fractures: a prospective randomized controlled trial.

BACKGROUND: The management of displaced intra-articular calcaneal fractures (DIACFs) remains challenging and controversial. A prospective randomized controlled trial was conducted to compare percutaneous reduction, cannulated screw fixation and calcium sulfate cement (PR+CSC) grafting with minimally invasive sinus tarsi approach and plate fixation (MISTA) for treatment of DIACFs. METHODS: Ultimately, 80 patients with a DIACFs were randomly allocated to receive either PR+CSC (N = 42) or MISTA (N = 38). Functional outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores. Radiological results were assessed using plain radiographs and computed tomography (CT) scans, and postoperative wound-related complications were also recorded. RESULTS: The average time from initial injury to operation and the average operation time in the PR+CSC group were both significantly shorter than those in the MISTA group (p < 0.05). There were significantly fewer complications in the PR+CSC group than those in the MISTA group (7.1 % vs 28.9 %, p < 0.001). The calcaneal width immediate postoperatively and at the final follow-up in the MISTA group were obviously improved compared to those in the PR+CSC group (p < 0.001). The variables of sagittal motion and hindfoot motion of the AOFAS scoring system in the PR+CSC group were significantly higher than those in the MISTA group (p < 0.05). The good and excellent results in the two groups were comparable for Sanders Type-II calcaneal fractures, but the good to excellent rate in the MISTA group was significantly higher for Sanders Type-III fractures (p < 0.05). CONCLUSION: The clinical outcomes are comparable between the two minimally invasive techniques in the treatment of Sanders Type-II DIACFs. The PR+CSC grafting is superior to the MISTA in terms of the average time between initial injury and operation, operation time, wound-related complications and subtalar joint activity. However, the MISTA has its own advantages in improving the calcaneal width, providing a more clear visualization and accurate reduction of the articular surface, especially for Sanders Type-III DIACFs. TRIAL REGISTRATION: ChiCTRIOR16008512 . 21 May 2016.

Effects of Traditional Chinese Medicine Huangqi Injection (Radix astragali) on Random Skin Flap Survival in Rats.

BACKGROUND: Huangqi (Radix astragali) is a traditional Chinese drug, designed to "buqi," which means invigorating vital energy, widely used in clinical settings. We investigated the effect of Huangqi injection on the survival of random skin flaps. METHODS: McFarlane flaps were established in 60 rats divided into two groups. Postoperative celiac injections were given to both groups for 7 days. Huangqi was injected into the test group, and saline was injected into controls. On day 7, tissues were stained with hematoxylin and eosin, immunohistochemically evaluated, and the expression levels of xanthine oxidase determined. RESULT: The mean area of flap survival in the test group was significantly higher compared with the controls. Expression of vascular endothelial growth factor and superoxide dismutase, and microvessel development, were markedly increased in the test group, and the malondialdehyde level was reduced. CONCLUSION: Huangqi injection promotes random skin flap survival.

Effects of traditional Chinese medicine Shuxuetong injection on random skin flap survival in rats.

BACKGROUND: A Shuxuetong injection is traditionally used in Chinese medicine to treat "blood stasis and stagnation" (yu xue yu zhi). We investigated the effect of such injection on the survival of random skin flaps. METHODS: McFarlane flaps were established in 60 rats divided into two groups. Postoperative celiac injections were given to both groups for 7 days. Shuxuetong was injected into the test group, and saline was injected into controls. On day 7, tissues were stained with H&E (hematoxylin-eosin) stain, immunohistochemically evaluated, and the expression levels of xanthine oxidase were determined. RESULT: The mean area of flap survival in the test group was significantly higher than in controls. Expression of vascular endothelial growth factor and superoxide dismutase, and microvessel development, were markedly increased in the test group, and the malondialdehyde level was reduced. CONCLUSION: Shuxuetong promotes random skin flap survival.