Objective: To evaluate the effect of nickel-titanium three-dimensional memory alloy mesh combined with autologous bone for living model of canine tibial plateau collapse fracture by biomechanical testing. Methods: Sixteen healthy 12-month-old Beagle dogs were randomly divided into 4 group, 4 dogs in each group. The dogs were used to establish the tibial plateau collapse fracture model in groups A, B, and C. Then, the nickel-titanium three-dimensional memory alloy mesh combined with autologous bone (the fibula cortical bone particles), the artificial bone (nano-hydroxyapatite), and autologous fibula cortical bone particles were implanted to repair the bone defects within 4 hours after modeling in groups A, B, and C, respectively; and the plate and screws were fixed outside the bone defects. The dogs were not treated in group D, as normal control. At 5 months after operation, all animals were sacrificed and the tibial specimens were harvested and observed visually. The destructive axial compression experiments were carried out by the biomechanical testing machine. The displacement and the maximum failure load were recorded and the axial stiffness was calculated. Results: All animals stayed alive after operation, and all incisions healed. After 1-3 days of operation, the animals could stand and move, and no obvious limb deformity was found. The articular surfaces of the tibial plateau specimens were completely smooth at 5 months after operation. No obvious articular surface collapse was observed. The displacement and maximum failure load of specimens in groups A and D were significantly higher than those in groups B and C ( P<0.05). But no significant difference was found between groups A and D and between groups B and C ( P>0.05). Conclusion: The nickel-titanium three-dimensional memory alloy mesh combined with autologous bone for subarticular bone defect of tibial plateau in dogs has good biomechanical properties at 5 months after operation, and has better axial stiffness when compared with the artificial bone and autologous bone graft.

The relationship between the conformation of interferon-α (IFN-α) and its anti-viral activity were analyzed by circular dichroism (CD) and flow cytometry (FCM) techniques. The recombinant human IFN-α (rIFN-α2b and rIFN-α2a) were used. CD spectra from 190 nm to 240 nm indicated that two the IFN-α showed stable secondary structure at 65 degrees C, but unstable when the temperature was above 65 degrees C, and the change was irreversible. FCM data of the anti-viral activity of IFN-α indicated that the change of its secondary structures partly weakened its anti-viral activity. The rIFN-α2b and rIFN-α2a showed the same phenomenon. These data indicated that the conformation of IFN-α is one of the factors to influence its anti-viral activity and the combination of CD and FCM is a good method to analyze the relationship between the conformation of protein drugs and their biological activities in single cell level.
Antiviral Agents ; chemistry ; Circular Dichroism ; Flow Cytometry ; Humans ; Interferon-alpha ; chemistry ; Protein Structure, Secondary ; Recombinant Proteins ; chemistry

Objective: To explore the effects of minimally invasive intracranial hematoma removal in the treatment of cerebral hemorrhage, and its influence on neurological functional recovery, serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-8(IL-8), tumor necrosis factor-alpha (TNF-α). Methods: From January 2016 to December 2017, 100 patients with cerebral hemorrhage admitted to Zhejiang Xin'an International Hospital were selected and randomly divided into two groups according to the digital table, with 50 cases in each group.The control group was given routine symptomatic treatment, the observation group received minimally invasive intracranial hematoma removal combined with conventional treatment.The curative effect, restoration of nerve function, the levels of hs-CRP, IL-6, IL-8 and TNF- were observed in the two groups. Results: After treatment, the blood loss and edema volume around the hematoma in the two groups were declined significantly (t=5.74, 9.32, 7.41, 9.32, all P<0.05), and the improvements of the observation group was better than those of the control group (t=8.29, 5.28, all P<0.05). The excellent and good rate of the observation group was 90%(45/50), which was significantly higher than 72%(36/50) of the control group (χ²=3.62, P<0.05). After treatment, the NDS scores of the two group were significantly lower than those before treatment (t=4.64, 5.75, all P<0.05), the GCS scores of the two groups were significantly improved (t=5.41, 7.86, all P<0.05). The NDS score of the observation group was significantly lower than that of the control group (t=5.31, P<0.05), the GCS score of the observation group was significantly higher than that of the control group(t=3.84, P<0.05). After treatment, the levels of inflammatory factors in the two groups were significantly reduced compared with those before treatment (t=3.27, 3.75, 3.38, 3.61, 5.74, 4.39, 6.52, 8.26, all P<0.05), the levels of inflammatory factors in the observation group were significantly lower than those in the control group (t=4.37, 3.92, 8.52, 4.28, all P<0.05). Conclusion Minimally invasive removal of intracranial hematoma combined with conventional treatment in the treatment of patients with cerebral hemorrhage can obtain satisfactory clinical effect, can promote neural functional recovery, improve inflammatory factor levels (hs-CRP, IL-6, IL-8, TNF alpha), it is worthy of application.

Aim To investigate the relation between the effect of geniposide (GE) in improving angiogenesis in arthralgia spasm syndrome collagen induced arthritis (CIA) rats and the modulation of heat shock proteins 70 (HSP70) release. Methods A CIA model was constructed by multiple intradermal injections of complete Freund's adjuvant (CFA) and an equal volume mixture of chicken type II collagen (CCII) into the dorsal and caudal root regions of rats, on the basis of which a rheumatic fever stimulus was given to build up a moist heat arthralgia spasm syndrome in CIA rats. After successful modeling, the groups were randomly grouped, and the administered groups were gavaged with GE (60, 120 mg · kg

Objective:To investigate the clinical efficacy of a medial support plate and a row of screws in the treatment of Schatzker type Ⅳ tibial plateau fracture involving the postero-lateral condyle.Methods:A retrospective analysis was performed of the data of 26 patients who had been admitted to Department of Orthopedic Trauma, Honghui Hospital Affiliated to Xi'an Jiaotong University for Schatzker type Ⅳ tibial plateau fracture involving the postero-lateral condyle from December 2015 to December 2020. There were 17 males and 9 females, aged from 19 to 51 years (average, 36.1 years). All their fracture lines involved the postero-lateral condyle and all fractures were fixated with a medial support plate and a row of screws via one medial and one lateral incisions. Recorded were the operation time, hospital stay, blood loss, incision length, fracture healing, complications, quality of knee joint reduction and knee joint function at the last follow-up.Results:The length of hospital stay ranged from 8 to 16 days, averaging 10.4 days. The 26 patients were followed up for 8 to 18 months, with an average of 14.3 months. All the fractures got united after 11 to 17 weeks (average, 13.7 weeks). During the follow-up, no reduction loss, internal fixation failure or surgical complications were observed. Rasmussen radiographic scores at the last follow-up ranged from 11 to 18 points, averaging 16.1 points. The range of motion of the knee joint ranged from 0° to 140°, averaging 120.8°. The Rasmussen scores of the knee function ranged from 14 to 28 points, averaging 24.4 points.Conclusion:In the treatment of Schatzker type Ⅳ tibial plateau fracture involving the postero-lateral condyle, the use of a medial support plate and a row of screws can achieve satisfactory clinical results.

Sphingosine 1-phosphate(SIP) is an important signal molecule produced by the metabolism of cell membrane sphingomyelin. SIP can be transported to the extracellular domain, and plays a role in activating a series of downstream signals, such as Ras/RafyERK, PI3K/AKT, by acting on SIP receptors. It can also act as a second messenger directly on intracellular targets such as HDAC, TRAF2. Its mediated signaling pathway plays a role in many physiological and pathological processes such as cell proliferation and migration, inflammatory cytokine infiltra tion, angiogenesis and autoimmunity. This article explores the role of SIP and its signaling pathways in inflammation-related diseases from the extracellular and intracellular roles of SIP, and reviews the research progress of SI P signaling pathway related drugs.

Based on the network target approach and technology, this study proposed for the first time a novel optimization method for Chinese medicine formulae. Moreover, with Qingluo Decoction as an example, a method for the research and development of Chinese medicine, which combines scientific methodology and experience of famous doctors, was developed. Specifically, based on the composition of Qingluo Decoction, this study used the using network target for intelligent and quantitative analysis on drug actions(UNIQ) to predict the medicinals that targeted the key pathways of rheumatoid arthritis(RA) such as angiogenesis. Then, combining the experience of the first national Chinese medical master LI Ji-ren and Aihui famous Chinese medicine doctor LI Yan and Chinese medicine theory, this study developed a novel angiogenesis-targeted prescription modified Qingluo Decoction(MQLD). Afterward, the clinical efficacy and mechanism of MQLD were verified. The results showed that 27 medicinals with significant regulatory effect on angiogenesis-related key signaling pathways were identified by UNIQ, among which 6 were selected by the Chinese medicine physicians to develop the MQLD. Clinical trials demonstrated that the clinical efficacy of MQLD, in terms of either American College of Rheumatology 20% improvement and 50% improvement criteria(ACR20, ACR50) or TCM syndrome evaluation, was better than that of Qingluo Decoction. Experimental study revealed that MQLD can inhibit RA angiogenesis by acting on the vascular endothelial growth factor(VEGF) pathway, nuclear factor κB(NF-κB) pathway, inflammatory cytokine release, and immune cell regulation. Taken together, this study developed a new formula MQLD with improved clinical efficacy, precise applicable clinical settings, and authorized patent through the network target technology, thus providing a new way for the precise development of Chinese medicine and preservation of the experience of famous physicians.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Vascular Endothelial Growth Factor A ; Prescriptions ; Physicians

To investigate the " drug-guide" effect of Achyranthes bidentata saponins( ABS) and geniposide( GE) in the treatment on adjuvant arthritis( AA) rats. A UHPLC-MS/MS method for the quantitative determination of GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa in rat blood and joint dialysate was established. After single or combined administration with ABS and GE was given to AA rat model,a microdialysis sampling method for rat joint cavity and jugular vein blood vessels was established to collect microdialysis samples. Waters Acquity HSS C_(18) column was used to separate the above four components,with mobile phase as acetonitrile-0. 1% formic acid water as mobile phase for gradient elution. ESI source was adopted for mass spectra in a negative ion scanning mode. Multiple reaction monitoring( MRM) mode was applied to detect the above four components. The methodological results showed that GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa demonstrated a good linear relationship within the concentration ranges of 2-4 000,16-4 096,14-3 584,23-5 888 μg·L-1 respectively. The precision,accuracy,stability and matrix effect of these four ingredients reached the requirements of quantitative analysis of biological samples. The pharmacokinetic results demonstrated that the combined administration of ABS and GE( 60 mg·kg~(-1)+60 mg·kg~(-1)) can increase the degree of GE in joint cavity distribution,and the AUCjoint/AUCplasmwere twice of that of single administration of GE( 60 mg·kg~(-1)),which indicated that ABS might played a vital role in GE's distribution to joint cavity. Moreover,there was no significant difference between the distribution trend of total three ABS and GE in rats. The pharmacodynamics results showed that the combined administration of ABS and GE has stronger effects on paw swelling,arthritis index and synovial pathomorphology of AA rats than single administration of GE,which suggested that ABS might improve GE's anti-inflammatory effect in AA rats. Based on the above results,ABS has a targeting effect in increasing GE's concentration in joint cavity,with a synergy in efficacy.
Achyranthes ; chemistry ; Animals ; Arthritis, Experimental ; drug therapy ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; pharmacokinetics ; Iridoids ; pharmacokinetics ; Microdialysis ; Rats ; Reproducibility of Results ; Saponins ; pharmacokinetics ; Tandem Mass Spectrometry

The purpose of this study was to explore the improving effect of Anshen Dingzhi Prescription (ADP) on Alzheimer's disease (AD)-like behavior in mice and its mechanisms. The main chemical components of ADP were identified by ultra performance liquid chromatography-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The AD-like mouse model was induced by D-galactose (D-gal) combined with Aβ_1-42 oligomer (AβO). The effect of ADP on AD-like behavior in mice was assessed using various behavioral experiments; pathomorphological changes in mouse hippocampal tissue were observed by Nissl staining and transmission electron microscopy; ELISA was used in the assessment of oxidative stress factors and inflammation-related factor levels; Western blot was performed to detect the expression of Aβ, Tau and glial fibrillary acidic protein (GFAP) proteins. The active components of ADP were screened according to TCMSP and HERB database, and the action targets of active components were predicted by Swiss Target Prediction platform. In addition, the targets of AD were predicted through DisGeNET database. Further, GO and KEGG enrichment analysis of common targets was carried out by Metascape database. Combined with the results of GO and KEGG analysis, in vivo experiments were carried out to explore the potential mechanism of ADP improving AD-like behavior in mice from the PI3K/Akt, calcium signal pathway and synaptic function. Finally, the core components of ADP were molecularly docked to the validated targets using Autodock Vina. Animal experiments were approved by the Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2021080). The results showed that the five chemical components, including ginsenoside Rg1, ginsenoside Rb1, tenuifolin, poricoic acid B and α-asarone were found in the ADP. ADP significantly improved the anxiety-like behavior and memory impairment, protected hippocampal neurons, decreased the levels of oxidative stress and inflammation, and inhibited the expression of Aβ and p-Tau induced by D-galactose combined with AβO in mice. The results of network pharmacology suggested that PI3K/Akt, calcium signal pathway and cell components related to postsynaptic membrane might be the key factors for ADP to improve AD. Animal experiments revealed that ADP up-regulated N-methyl-D-aspartate receptor 2A (GluN2A), postsynaptic density protein 95 (PSD95), calpain-1, phosphorylated protein kinase B (p-Akt), phosphorylated cAMP response element binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) expression and inhibited p-GluN2B and calpain-2 expression in the hippocampus of AD-like mice. The molecular docking results demonstrated that the core components of ADP, such as panaxacol, dehydroeburicoic acid, deoxyharringtonine, etc. had a high binding ability with the validated targets GRIN2A, GRIN2B, PSD95, etc. In summary, our results indicate ADP improves AD-like pathological and behavioral changes induced by D-galactose combined with AβO in mice, and the mechanism might be related to the NMDAR/calpain axis and Akt/CREB/BDNF pathway.

Aim To use microdialysis technology combined with ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technology to study the effect of Achyranthes bidentata saponins (ABS) on rheumatoid arthritis (RA) and its mechanisms. Methods SD rats were randomly divided into adjuvant arthritis (AA) model group, blank control group and ABS administration group. AA rat model was induced by Freund's complete adjuvant. UPLC-Q-TOF/MS was used to collect joint cavity microdialysis fluid sample information of each group of rats. Results On 6th day after administration of ABS, an inhibitory effect on the paw swelling, improved the arthritis score (P < 0. 05), and better the pathological morphology of the synovial tissues were found in AA rats. Nineteen potential biomarkers were discovered and identified. Pathway enrichment analysis revealed that they mainly involved purine metabolism, pyrimidine metabolism, fatty acid biosynthesis and steroid hormone biosynthesis pathway. Conclusions Microdialysis combined with metabolomics can reveal the metabolic mechanism of ABS intervention on RA, laying a foundation for further study of the mechanism of ABS.