Direct Radiological Visualization of Loading on Four Flexor Tendon Repair Suture Configurations.

PURPOSE: To study the deformation of 4 suture configurations used in flexor tendon repair using fluoroscopy. METHODS: All flexor tendon repair techniques have a longitudinal component, a link component, and/or a transverse component. We had previously described 4 types of link components, namely an arc (grasping loop), a simple loop (locking loop), a complex loop, and a knot. The effect of loading on suture configurations using each of these link components was tested in flexor tendon from the first ray of porcine feet. Forty flexor tendons were divided into 4 groups of 10 each, and one-half of a tendon repair was simulated on each group using 0.5 mm stainless steel wire. The tendons were mounted on a materials testing machine, and tensile force was applied until failure. The deformation of the suture within the tendon substance was observed using an image intensifier, and the maximal load to failure was measured. RESULTS: The loading of the suture led to unraveling of the suture in an arc, constriction and unraveling in a simple loop, and initial constriction with no further change of the construct in the complex loop with no change in the knot design. The mean pullout strength of the complex loop was statistically greater than all the other 3 designs. CONCLUSIONS: Each of the link component designs demonstrated unique deformation characteristics. The complex loop design had the strongest grasping ability. CLINICAL RELEVANCE: This study identified the differences in the deformation characteristics of the 4 types of link components used in flexor tendon repair. This knowledge may allow for the development of better flexor tendon repair techniques and the adoption of a more precise classification of flexor tendon repair techniques.

Neuroprotective Effect and Mechanism of Tanreqing Injection on Ischemic Stroke: Insights from Network Pharmacology and in vivo Experiments.

OBJECTIVE: To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation. METHODS: The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions. RESULTS: We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P<0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P<0.05). In addition, 41 chemical compounds in TRQ could bind to APJ. CONCLUSIONS: The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings.

Evaluation of eleven kiwifruit genotypes for bicarbonate tolerance and characterization of two tolerance-contrasting genotypes.

Screening bicarbonate-tolerant genotypes is an environmentally-friendly and long-term effective strategy to cope with bicarbonate-induced chlorosis in fruit crops grown on calcareous soils. We investigated eleven genotypes from four kiwifruit species (Actinidia chinensis, A. macrosperma, A. polygama, and A. valvata) for differences in bicarbonate tolerance. We also characterized the physiological and molecular differences in two contrasting genotypes of this group. In the first experiment, bicarbonate-treated plantlets were irrigated with 3.0 g L-1 CaCO3 and 5.04 g L-1 NaHCO3 in peat and perlite medium culture. Based on principal component analysis, weight-based membership function method and cluster analysis, the tested genotypes were classified into three groups: (1) tolerant, including YX, Av-1, Acd, Ap, Av-2, and QM; (2) moderately tolerant, including Av-3, Am, Av-4, and HWD; and (3) sensitive, including only QH. In the second experiment, QH (bicarbonate-sensitive) and YX (bicarbonate-tolerant) were grown in sand culture with 4.0 g L-1 CaCO3 and 0.84 g L-1 or 1.26 g L-1 NaHCO3. Compared with QH, YX showed a better ability to take up iron (Fe) by roots and to transport Fe from roots to shoots in the bicarbonate treatments, probably due to a better capacity to protect from oxidative damage and to excrete protons, and a differential expression of genes associated with Fe uptake and translocation, including HA8, IRT1, YSL3 and NRAMP3. The results can facilitate identifying potential resources for bicarbonate tolerance and breeding new rootstocks, and contribute to the elucidation of the bicarbonate tolerance mechanisms in the genus Actinidia.

The Neuroprotective Effect of Shenmai Injection on Oxidative Stress Injury in PC12 Cells Based on Network Pharmacology.

Background: Shenmai injection (SMI) has been used in the treatment of cerebrovascular diseases and cardiovascular diseases. However, the underlying mechanism of SMI for neuroprotection after acute ischemic stroke (AIS) remains unclear. This study aimed to explore the potential molecular mechanism of SMI in treating reperfusion injury after AIS and its protective effect on PC12 cells against oxidative stress through in vitro experiments based on network pharmacological predictions. Methods: The network pharmacology method was used to collect the compounds in SMI and AIS damage targets, construct the "drug-disease" target interaction network diagram, screen the core targets, and predict the potential mechanism of SMI treatment of AIS. In addition, the oxidative stress model of PC12 cells was induced by H2O2 to evaluate the neuroprotective effect and predictive mechanism of SMI on PC12 cells. Results: A component-targeted disease and functional pathway network showed that 24 components from SMI regulated 77 common targets shared by SMI and AIS. In PC12 cells damaged by H2O2, SMI increased cell survival, alleviated oxidative stress injury, prevented cell apoptosis, and increased the expression of APJ, AMPK, and p-GSK-3ß. After Si-APJ silenced APJ expression, the above protective effect of SMI was significantly weakened. Conclusion: SMI is characterized by multiple components, multiple targets, and multiple pathways and inhibits oxidative stress and alleviates nerve injury induced by H2O2 through regulating the APJ/AMPK/GSK-3ß pathway.

Chinese herbal injections combined with rt-PA intravenous thrombolysis for acute ischemic stroke: A systematic review and meta-analysis protocol.

BACKGROUND: Acute ischemic stroke (AIS) is an important factor leading to adult death and disability globally. For AIS patients who meet certain conditions, recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis is an important method recommended by national guidelines to achieve vascular recanalization. However, complications such as hemorrhagic transformation and vascular reocclusion after thrombolysis are still unsolved problems in clinical. Several systematic reviews of clinical randomized controlled trials (RCTs) in the past have shown that Chinese herbal injections (CHIs) can improve the neurological function of patients, increase the tolerance of ischemic tissues to hypoxia, and inhibit platelet aggregation. Therefore, this study conducted a meta-analysis of AIS treatment with intravenous thrombolysis alone and compared it with the combined application of CHIs. To evaluate whether CHIs have a synergistic effect on thrombolytic therapy and provide a basis for clinical application. METHODS: The following databases will be searched until September 2020: ①English databases: PubMed, Cochrane Library, Embase; ②Chinese databases: CNKI, Wanfang database, Weipu database, SinoMed. RCTs will be included to compare the efficacy of thrombolysis combined with CHIs and thrombolysis alone in the treatment of AIS. Data extraction and risk of bias assessments will be carried out by 2 verifiers independently. The risk of bias will be evaluated through the Cochrane risk of bias tool. Review Manager software 5.3 will be used for statistical analysis. RESULTS: This study will provide comprehensive evidence for the treatment of AIS by CHIs combined with intravenous thrombolysis from multiple aspects. CONCLUSION: The conclusion of the meta-analysis will provide a basis for judging whether CHIs combined with intravenous thrombolysis is an effective measure for the treatment of AIS. ETHICS AND DISSEMINATION: Ethical approval is not needed because this study will be based on data that already published. We will publish the findings of this study in a peer-reviewed journal and related conferences. PROSPERO REGISTRATION NUMBER: CRD42020215546.

Randomized controlled trial comparing the effectiveness of mass and spaced learning in microsurgical procedures using computer aided assessment.

Spaced-learning refers to teaching spread over time, compared to mass-learning where the same duration of teaching is completed in one session. Our hypothesis is that spaced-learning is better than mass-learning in retaining microsurgical suturing skills. Medical students were randomized into mass-learning (single 8-h session) and spaced-learning (2-h weekly sessions over 4 weeks) groups. They were taught to place 9 sutures in a 4 mm-wide elastic strip. The primary outcome was precision of suture placement during a test conducted 1 month after completion of sessions. Secondary outcomes were time taken, cumulative performance, and participant satisfaction. 42 students (24 in the mass-learning group; 18 in spaced-learning group) participated. 3 students in the spaced-learning group were later excluded as they did not complete all sessions. Both groups had comparable baseline suturing skills but at 1 month after completion of teaching, the total score for suture placement were higher in spaced-learning group (27.63 vs 31.60,p = 0.04). There was no statistical difference for duration and satisfaction in either group. Both groups showed an improvement in technical performance over the sessions, but this did not differ between both groups. Microsurgical courses are often conducted in mass-learning format so spaced learning offers an alternative that enhances retention of complex surgical skills.

Direct and Bicarbonate-Induced Iron Deficiency Differently Affect Iron Translocation in Kiwifruit Roots.

Bicarbonate-induced iron (Fe) deficiency (+Bic) is frequently observed in kiwifruit orchards, but more research attention has been paid to direct Fe deficiency (-Fe) in plants, including kiwifruit. Here we compared the differences of kiwifruit plants between -Fe and +Bic in: (1) the traits of 57Fe uptake and translocation within plants, (2) Fe forms in roots, and (3) some acidic ions and metabolites in roots. The concentration of 57Fe derived from nutrient solution (57Fedfs) in roots was less reduced in +Bic than -Fe treatment, despite similar decrease in shoots of both treatments. +Bic treatment increased 57Fedfs distribution in fine roots but decreased it in new leaves and stem, thereby displaying the inhibition of 57Fedfs translocation from roots to shoots and from fine roots to xylem of coarse roots. Moreover, +Bic imposition induced the accumulation of water-soluble Fe and apoplastic Fe in roots. However, the opposite was observed in -Fe-treated plants. Additionally, the cell wall Fe and hemicellulose Fe in roots were less reduced by +Bic than -Fe treatment. +Bic treatment also triggered the reduction in H+ extrusion and the accumulation of NH4+, succinic acid, and some amino acids in roots. These results suggest that, contrary to -Fe, +Bic treatment inhibits Fe translocation to shoots by accumulating water-soluble and apoplastic Fe and slowing down the release of hemicellulose Fe in the cell wall in kiwifruit roots, which may be related to the decreased H+ extrusion and the imbalance between C and N metabolisms.

Xiaoyukang Jiaonang Promotes the Degradation of Hypoxia-Inducible Factor 1α and Antiangiogenesis and Anti-Inflammation in Chronic Subdural Hematoma Rat Model.

Xiaoyukang Jiaonang (XYK) is a Chinese patent medicine approved by the National Medical Product Administration which is used to treat intracranial hematoma in China. In this study, we observed the molecular mechanism of XYK in hypoxia-inducible factor 1α (HIF-1α), inflammation and angiogenesis of chronic subdural hematoma (CSDH). The CSDH model was made by using internal iliac vein blood of Wister rats, and rats were divided into sham group, CSDH group and XYK group. The rats in the XYK group were gavaged with Xiaoyukang Jiaonang (185 mg/kg) for 7 days, and rats in the CSDH group and sham group were gavaged with the same amount of physiological saline for 7 days. In the CSHD rat model, active inflammation and angiogenesis were observed around the hematoma. XYK promoted the ubiquitination and degradation of HIF-1α, and reduced the concentration of VEGF and the ratio of angiopoietin-1/angiopoietin-2. XYK reduced proinflammatory cytokines and increased anti-inflammatory cytokine. In tissue section, XYK reduced the size of the hematoma and membrane, and reduced vWF positive cells in membrane. Furthermore, the endothelial progenitor cells in blood decreased as well. Overall, XYK shows anti-inflammatory and antiangiogenesis effects which may relate to the degradation of HIF-1α.

Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials.

Recently, extensive researches about stem cell-based therapies for ischemic stroke have been published; our review evaluated the efficacy and safety of stem cell-based therapies for ischemic stroke. Our review was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42019135805. Two independent observers searched PubMed, EMBASE, Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials), and Web of Science (Science Citation Index Expanded) for relevant studies up to 31 May 2019. We included clinical trials which compared efficacy outcomes (measured by National Institutes of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), or Barthel index (BI)) and safety outcomes (such as death and adverse effects) between the stem cell-based therapies and control in ischemic stroke. We performed random effect meta-analysis using Review Manager 5.3. Our review included nine randomized controlled trials (RCTs) and seven non-randomized studies (NRSs), involving 740 participants. Stem cell-based therapies were associated with better outcomes measured by NIHSS (mean difference (MD) - 1.63, 95% confidence intervals (CI) - 2.73 to - 0.53, I2 =60%) and BI (MD 14.68, 95% CI 1.12 to 28.24, I2 = 68%) in RCTs, and by BI (MD 6.40, 95% CI 3.14 to 9.65, I2 = 0%) in NRSs. However, the risk of bias was high and the efficacy outcomes of RCTs were high heterogeneity. There was no significant difference in mortality between the stem cell group and the control group. Fever, headache, and recurrent stroke were the most frequently reported adverse effects. Our review shows that stem cell-based therapies can improve the neurological deficits and activities of daily living in patients with ischemic stroke.

Spraying rhubarb powder solution under gastroscope in the treatment of acute non-varicose upper gastrointestinal bleeding: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Systematically assessing the safety and effectiveness of spraying rhubarb powder solution under gastroscope for the treatment of acute non-varicose upper gastrointestinal bleeding, and confirmation for further clinical research and application. METHODS: We searched the following databases up till November 2019: PubMed, the Cochrane Library, EMBASE, CNKI, WanFang Data, VIP and SinoMed. Randomized controlled trials (RCTs) were used to compare the curative effect of spraying rhubarb powder solution with other drugs under gastroscope for the treatment of acute non-varicose upper gastrointestinal bleeding. RESULTS: Out of 171 articles, 14 RCTs involving 1493 patients were included. All control groups included in the RCTs were treated with norepinephrine solution. The hemostatic effect of spraying rhubarb powder solution under gastroscope was examined for 24 h at high concentration (0.1 g/mL). The hemostatic effect at higher conc. (0.1 g/mL) found far more better than low conc.(RR = 1.48;95 %CI:1.25,1.75;P﹤0.00001) (0.03 g/mL)as homeostatic effect at low conc.is same that of norepinephrine solution (RR = 1.02;95 %CI:0.94,1.10;P = 0.62). Moreover within 48 h, rhubarb powder solution with 0.1 g/mL or 0.15 g/mL conc. have of significantly higher hemostatic effects than norepinephrine solution (RR = 1.18;95 % CI: 1.08, 1.30;P = 0.0003). Occurrence of rebleeding event within 48 h after successful hemostasis (RR = 0.42;95 %CI:0.24,0.74;P = 0.003) reduced exceptionally. After that the hemostatic effect of rhubarb powder solution with 0.1 g/mL conc.examined within 72 h again exhibited significant improvement than norepinephrine solution (RR = 1.19;95 %CI:1.12,1.26;P < 0.00001). On par with immediate hemostasis time, rhubarb powder solution took unprecedented less time than norepinephrine solution;(MD=-5.56S;95 %CI:-6.16, -4.95;P﹤0.00001). Additionally, the adverse reaction produced by rhubarb powder solution is much lower than norepinephrine solution (RR = 0.22;95 %CI:0.11,0.42;P < 0.00001). CONCLUSIONS: According to meta-analysis, Spraying rhubarb powder solution under gastroscope in the treatment of acute non-varicose upper gastrointestinal bleeding is superior to norepinephrine solution in improving hemostasis effect. Shortening immediate hemostasis time and reducing rebleeding,and is safe to use. Based on the results of this study, physicians can treat patients with acute non-varicose upper gastrointestinal bleeding by spraying rhubarb powder solution under gastroscope according to the patients' condition.However, the sample size included in this study is small and of substandard quality qu, and a large sample size clinical trial with strict design and normative report is needed to verify the safety and efficacy of rhubarb powder solution under gastroscope for acute non-varicose upper gastrointestinal bleeding.

MnSOD is implicated in accelerated wound healing upon Negative Pressure Wound Therapy (NPWT): A case in point for MnSOD mimetics as adjuvants for wound management.

Negative Pressure Wound Therapy (NPWT), a widely used modality in the management of surgical and trauma wounds, offers clear benefits over conventional wound healing strategies. Despite the wide-ranging effects ascribed to NPWT, the precise molecular mechanisms underlying the accelerated healing supported by NPWT remains poorly understood. Notably, cellular redox status-a product of the balance between cellular reactive oxygen species (ROS) production and anti-oxidant defense systems-plays an important role in wound healing and dysregulation of redox homeostasis has a profound effect on wound healing. Here we investigated potential links between the use of NPWT and the regulation of antioxidant mechanisms. Using patient samples and a rodent model of acute injury, we observed a significant accumulation of MnSOD protein as well as higher enzymatic activity in tissues upon NPWT. As a proof of concept and to outline the important role of SOD activity in wound healing, we replaced NPWT by the topical application of a MnSOD mimetic, Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP5+, MnE, BMX-010, AEOl10113) in the rodent model. We observed that MnE is a potent wound healing enhancer as it appears to facilitate the formation of new tissue within the wound bed and consequently advances wound closure by two days, compared to the non-treated animals. Taken together, these results show for the first time a link between NPWT and regulation of antioxidant mechanism through the maintenance of MnSOD activity. Additionally this discovery outlined the potential role of MnSOD mimetics as topical agents enhancing wound healing.

Uncovering the Pharmacological Mechanism of Chaibei Zhixian Decoction on Epilepsy by Network Pharmacology Analysis.

OBJECTIVE: Epilepsy is a neuronal disorder that is characterized by epileptic seizures and linked with abnormal neural functioning in the brain. Traditional Chinese medicine (TCM) formula Chaibei Zhixian decoction (CZD) has been widely used for epilepsy in China while the pharmacological mechanisms are still unclear. In the present study, systematic and comprehensive network pharmacology was utilized for the first time to reveal the potential pharmacological mechanisms of CZD on epilepsy. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis platform was utilized for the development of an ingredients-targets database. After identifying epileptic targets of CZD, their interaction with other proteins was estimated based on protein-protein interaction network created from STITCH and gene ontology (GO) enrichment analysis utilizing Cytoscape-ClueGO plugin. RESULTS: CZD formula was found to have 643 chemical ingredients, and the potential protein targets of these ingredients were 5230, as retrieved from TCMSP database. Twenty-six protein targets were found to be associated with epilepsy. Thirteen hub genes were regulated by CZD in epilepsy, including estradiol, ESR1, ESR2, SRC, CTNNB1, EP300, MAPK1, MAPK3, SP1, BRCA1, NCOA3, CHRM1, and GSK3B. The results of GO terms analysis showed that 8 GO terms were recovered in the form of 3 clusters, including negative regulation of protein kinase B signaling, positive regulation of interleukin-1 production, and microvillus assembly. CONCLUSIONS: Network pharmacology approach provides better understanding of the underlying pharmacological mechanisms of CZD on epilepsy. Estradiol, ESR1, ESR2, CTNNB1, EP300, MAPK1, MAPK3, BRCA1, and GSK3B are likely to be important molecules regulated by CZD in treatment of epilepsy. Negative regulation of protein kinase B signaling may play vital roles in the treatment of epilepsy by CZD.