Motor learning changes the axon initial segment of the spinal motoneuron.

We are studying the mechanisms of H-reflex operant conditioning, a simple form of learning. Modelling studies in the literature and our previous data suggested that changes in the axon initial segment (AIS) might contribute. To explore this, we used blinded quantitative histological and immunohistochemical methods to study in adult rats the impact of H-reflex conditioning on the AIS of the spinal motoneuron that produces the reflex. Successful, but not unsuccessful, H-reflex up-conditioning was associated with greater AIS length and distance from soma; greater length correlated with greater H-reflex increase. Modelling studies in the literature suggest that these increases may increase motoneuron excitability, supporting the hypothesis that they may contribute to H-reflex increase. Up-conditioning did not affect AIS ankyrin G (AnkG) immunoreactivity (IR), p-p38 protein kinase IR, or GABAergic terminals. Successful, but not unsuccessful, H-reflex down-conditioning was associated with more GABAergic terminals on the AIS, weaker AnkG-IR, and stronger p-p38-IR. More GABAergic terminals and weaker AnkG-IR correlated with greater H-reflex decrease. These changes might potentially contribute to the positive shift in motoneuron firing threshold underlying H-reflex decrease; they are consistent with modelling suggesting that sodium channel change may be responsible. H-reflex down-conditioning did not affect AIS dimensions. This evidence that AIS plasticity is associated with and might contribute to H-reflex conditioning adds to evidence that motor learning involves both spinal and brain plasticity, and both neuronal and synaptic plasticity. AIS properties of spinal motoneurons are likely to reflect the combined influence of all the motor skills that share these motoneurons. KEY POINTS: Neuronal action potentials normally begin in the axon initial segment (AIS). AIS plasticity affects neuronal excitability in development and disease. Whether it does so in learning is unknown. Operant conditioning of a spinal reflex, a simple learning model, changes the rat spinal motoneuron AIS. Successful, but not unsuccessful, H-reflex up-conditioning is associated with greater AIS length and distance from soma. Successful, but not unsuccessful, down-conditioning is associated with more AIS GABAergic terminals, less ankyrin G, and more p-p38 protein kinase. The associations between AIS plasticity and successful H-reflex conditioning are consistent with those between AIS plasticity and functional changes in development and disease, and with those predicted by modelling studies in the literature. Motor learning changes neurons and synapses in spinal cord and brain. Because spinal motoneurons are the final common pathway for behaviour, their AIS properties probably reflect the combined impact of all the behaviours that use these motoneurons.

Does mild flexion of the femoral prosthesis in total knee arthroplasty result in better early postoperative outcomes?

BACKGROUND: The purpose of this study was to measure the femoral prosthesis flexion angle (FPFA) in total knee arthroplasty (TKA) using three-dimensional reconstruction, and to assess the differences in early clinical efficacy between patients with different degrees of flexion. METHODS: We conducted a prospective cohort study. From June 2019 to May 2021, 113 patients admitted for TKA due to osteoarthritis of the knee were selected. The patients' postoperative knee joints were reconstructed in three dimensions according to postoperative three-dimensional computed tomography (CT) scans. The FPFA was measured, and the patients were divided into 4 groups: anterior extension group (FPFA < 0°), mildly flexed group (0° ≤ FPFA < 3°), moderately flexed group (3° ≤ FPFA < 6°) and excessively flexed group (6° ≤ FPFA). The differences in the Knee Society Score (KSS), knee Range of Motion (ROM), and visual analogue scale (VAS) scores were measured and compared between the four groups at each postoperative time point. RESULTS: Postoperative KSS, ROM, and VAS were significantly improved in all groups compared to the preoperative period. At 1 year postoperatively, the ROM was significantly greater in the mildly flexed group (123.46 ± 6.51°) than in the anterior extension group (116.93 ± 8.05°) and the excessively flexed group (118.76 ± 8.20°) (P < 0.05). The KSS was significantly higher in the mildly flexed group (162.68 ± 12.79) than in the other groups at 6 months postoperatively (P < 0.05). The higher KSS (174.17 ± 11.84) in the mildly flexed group was maintained until 1 year postoperatively, with a statistically significant difference (P < 0.05). No significant difference in VAS scores was observed between groups at each time point. CONCLUSIONS: A femoral prosthesis flexion angle of 0-3° significantly improved postoperative knee mobility, and patients could obtain better Knee Society Scores after surgery, which facilitated the postoperative recovery of knee function. TRIAL REGISTRATION: ChiCTR2100051502, 2021/09/24.

Effect of bone cement sealing of the intramedullary femoral canal on coagulation status after total knee arthroplasty: a retrospective thromboelastography study.

BACKGROUND: The main objective of this study was to investigate whether the use of bone cement in total knee arthroplasty (TKA) has an effect on postoperative coagulation status and bleeding. METHODS: 153 patients who underwent unilateral TKA between September 2019 and February 2023 were collected and divided into Bone and Cement&Bone groups according to whether bone cement was used to seal the bone medullary canal intraoperatively. Routine blood and thromboelastography (TEG) examinations were performed on the day before, the first day and the seventh day after surgery; postoperative bleeding, drainage, transfusion rate and the number of people suffering from deep venous thrombosis (DVT) were recorded. RESULTS: There were no significant differences between the two groups in terms of baseline clinical characteristics before surgery (P > 0.05). In terms of TEG indicators, the coagulation index (CI) of the Bone&Cement group was lower than that of the Bone group on the first postoperative day and on the seventh postoperative day (P < 0.05). The CI of patients in the Bone group on the first postoperative day was lower than that of the preoperative day (P < 0.05); in terms of blood loss, the total blood loss and occult blood loss were lower in the Bone&Cement group than in the Bone group (P < 0.05). In addition, there was no significant difference in postoperative drainage,transfusion rate and the incidence of DVT between the two groups. CONCLUSION: Blocking the intramedullary canal of the femur with bone cement during TKA improves relative postoperative hypocoagulation and reduces postoperative blood loss, although there is no significant effect on transfusion rates, drainage and DVT.

Diagnostic value of mean platelet volume combined with thromboelastography for coagulation state after total knee arthroplasty.

BACKGROUND: The main objective of this study was to predict the status of blood and the occurrence of lower limb deep vein thrombosis (DVT) after total knee arthroplasty(TKA) by means of mean platelet volume (MPV) combined with thromboelastography (TEG). METHODS: We collected 180 patients who underwent unilateral total knee arthroplasty between May 2015 and March 2022, and the patients were divided into DVT group and control group according to whole-leg ultrasonography on the seventh postoperative day. Blood count and TEG were performed on the day before surgery, the first day after surgery and the seventh day respectively. Multifactorial analysis was used to investigate whether the relevant parameters were independent predictors of DVT after TKA. RESULTS: MPV has the strongest correlation with the maximum amplitude (MA), followed by alpha-angle; MPV and alpha-angle on the first postoperative day are independent predictors of DVT. MPV in patients with thrombosis tends to rise and then fall in the perioperative period. The optimal threshold for MPV to predict thrombosis is 10.85 fL and the area under the ROC curve is 0.694, The area under the ROC curve increases to 0.815 using MPV combined with alpha-angle. In addition, MA, α-angle, composite coagulation index (CI) and MPV were all statistically higher in the DVT group than in the control group (p < 0.001). CONCLUSION: MPV is a predictor of DVT after TKA. It can reflect the hypercoagulable state of blood after surgery; Combination of MPV and alpha-angle on the first day after surgery in patients with TKA improves predictive power of DVT.

[Ontologies Applied in Clinical Decision Support Systems for Diabetes].

A clinical decision support system (CDSS) integrated with electronic health records helps physicians at the grassroots make patient-appropriate and evidence-based treatment decisions and improves the efficiency of diagnosis and treatment. Furthermore, using ontologies to build up the medical knowledge base and patient data for CDSS enhances the automation and transparency of the reasoning process of CDSS and helps generate interpretable and accurate treatment recommendations. Herein, we reviewed the relevant ontologies in the field of diabetes treatment and the progress and challenges concerning ontology-based CDSSs. Firstly, we elaborated on the current status and challenges of diabetes treatment in China, highlighting the urgent need to improve the efficiency and quality of medical services. Then, we presented background information about ontologies and gave an overview of the framework, methodology, and features of using ontologies to construct CDSS. After that, we reviewed the ontologies and instances of ontology-based CDSS in the field of diabetes treatment in China and abroad and summarized their construction methods and features. Last but not the least, we discussed the future prospects of the field, suggesting that integrating evidence-based medicine with ontologies to build a reliable clinical recommendation system should be the current focus of CDSS development.

Different tibial rotational axes can be applied in combination according to the tibial tuberosity-posterior cruciate ligament distance in total knee arthroplasty.

PURPOSE: The purpose of this study was to investigate whether tibial tuberosity-posterior cruciate ligament (TT-PCL) distance is representative of the true lateralization of tibial tuberosity in isolation and its influence on the accuracy of the Akagi line and medial third of the tibial tuberosity (MTTT). METHODS: A total of 135 osteoarthritis patients with varus knees who undergoing computed tomography scans were enrolled to establish three-dimension models of the knees. Tibial width (TW), tibial tuberosity lateralization (TTL), posterior cruciate ligament lateralization (PCLL), knee rotation angle (KRA) and tibial rotational axes were measured and investigated their correlations with TT-PCL distance. Based on the analysis of receiver operating characteristic (ROC) curve, the influence of TT-PCL distance on the distributions of mismatch angles of tibial rotational axes was investigated with a safe zone (-5° to 10°). RESULTS: TT-PCL distance was in significantly positive correlation with TW (r = 0.493; P < 0.001) and TTL (r = 0.378; P < 0.001) which was different with PCLL (r = 0.147; P = 0.009) and KRA (r = -0.166; P = 0.054). All tibial rotational axes were significantly positively correlated with TT-PCL distance (P < 0.001). The mismatch angles between the vertical line of the surgical epicondylar axis (SEA) and the Akagi line and MTTT were -1.7° ± 5.3° and 7.6° ± 5.6° respectively. In terms of the optimal cut-off value of 19 mm for TT-PCL distance, the Akagi line applied as tibial rotational axis ensures 87.3% of the positions of tibial components within the safe zone when TT-PCL distance > 19 mm, and MTTT ensures 83.3% when TT-PCL distance ≤ 19 mm. CONCLUSION: TT-PCL distances cannot reflect the true lateralization of tibial tuberosity in isolation but can aid in the combination of the Akagi line and MTTT in varus knees. The patients with TT-PCL distance > 19 mm are recommended to reference the Akagi line for tibial rotational alignment. MTTT is recommended to the patients with TT-PCL distance ≤ 19 mm. The study will aid surgeons in deciding which reference may be used by measuring TT-PCL distance using a preoperative CT.

Gender differences affect the location of the patellar tendon attachment site for tibial rotational alignment in total knee arthroplasty.

PURPOSE: This study was carried out to investigate the accuracy of referring different locations of the patellar tendon attachment site and the geometrical center of the osteotomy surface for tibial rotational alignment and observe the influences of gender differences on the results. METHODS: Computed tomography scans of 135 osteoarthritis patients (82 females and 53 males) with varus deformity was obtained to reconstruct three-dimensional (3D) models preoperatively. The medial boundary, medial one-sixth, and medial one-third of the patellar tendon attachment site were marked on the tibia. These points were projected on the tibial osteotomy plane and connected to the geometrical center (GC) of the osteotomy plane or the middle of the posterior cruciate ligament (PCL) to construct six tibial rotational axes (Akagi line, MBPT, MSPT1, MSPT2, MTPT1 and MTPT2). The mismatch angle between the vertical line of the SEA projected on the proximal tibial osteotomy surface and six different reference axes was measured. In additional, the effect of gender differences on rotational alignment for tibial component were assessed. RESULTS: Relative to the SEA, rotational mismatch angles were - 1.8° ± 5.1° (Akagi line), - 2.5° ± 5.3° (MBPT), 2.8° ± 5.3° (MSPT1), 4.5° ± 5.4° (MSPT2), 7.3° ± 5.4° (MTPT1), and 11.6° ± 5.8° (MTPT2) for different tibial rotational axes in all patients. All measurements differed significantly between the male and female. The tibial rotational axes with the least mean absolute deviation for the female or male were Akagi line or MSPT, respectively. There was no significant difference in whether the GC of the osteotomy surface or the midpoint of PCL termination was chosen as the posterior anatomical landmark when the medial boundary or medial one-sixth point of the patellar tendon attachment site was selected as the anterior anatomical landmark. CONCLUSION: When referring patellar tendon attachment site as anterior anatomical landmarks for tibial rotational alignment, the influence of gender difference on the accuracy needs to be taken into account. The geometric center of the tibial osteotomy plane can be used as a substitute for the middle of the PCL termination when reference the medial boundary or medial one-sixth of the patellar tendon attachment site.

Stress distribution patterns during the gait cycle in patients with anterior femoral notching following total knee replacement.

BACKGROUND: Anterior femoral notching (AFN) is a severe complication of total knee replacement (TKR), which in a percentage of patients may lead to fractures after surgery. The purpose of this study was to investigate the stress distribution in patients with AFN and the safety depth of AFN during the gait cycle. METHODS: We performed a finite element (FE) analysis to analyse the mechanics around the femur during the gait cycle in patients with AFN. An adult volunteer was selected as the basis of the model. The TKR models were established in the 3D reconstruction software to simulate the AFN model during the TKR process, and the 1 mm, 2 mm, 3 mm, 4 mm, and 5 mm AFN models were established, after which the prosthesis was assembled. Three key points of the gait cycle (0°, 22°, and 48°) were selected for the analysis. RESULTS: The stress on each osteotomy surface was stable in the 0° phase. In the 22° phase, the maximum equivalent stress at 3 mm was observed. In the 48° phase, with the increase in notch depth, each osteotomy surface showed an overall increasing trend, the stress range was more extended, and the stress was more concentrated. Moreover, the maximum equivalent force value (158.3 MPa) exceeded the yield strength (115.1 MPa) of the femur when the depth of the notch was ≥ 3 mm. CONCLUSIONS: During the gait cycle, if there is an anterior femoral cortical notch ≥ 3 mm, the stress will be significantly increased, especially at 22° and 48°. The maximum equivalent stress exceeded the femoral yield strength and may increase the risk of periprosthetic fractures.

Early Stage Versus Late Stage Periarticular Injection during Unicompartmental Knee Arthroplasty for Postoperative Pain Relief: A Randomized Controlled Trial.

Controlling postoperative pain after unicompartmental knee arthroplasty (UKA) is essential to improve patient satisfaction and promote early recovery. The purpose of this study was to investigate the difference in clinical efficacy between early and late stage periarticular injection during UKA for postoperative pain relief. Eighty-four patients meeting the inclusion and exclusion criteria were randomly divided into the early stage periarticular injection group and late stage periarticular injection group by using a random number tables method. The difference between the two groups was that the early stage periarticular injection group received superficial injection before the joint incision, while the late stage periarticular injection group received superficial injection after implantation of the prosthesis. Deep injection and other perioperative conditions of the two groups were controlled identically. The primary outcome of the study was the recovery room immediate visual analog scale (VAS) at rest. The secondary outcomes were the postoperative VAS (at rest) at 3, 6, 9, 12, 18, 24, 48, 72, 96, and 120 hours, drug dosage of rescue analgesia, range of motion (ROM), and complications. The recovery room immediate VAS (at rest) in the early stage periarticular injection group was significantly lower than that of the late stage periarticular injection group (21 ± 24 vs. 32 ± 34 mm, p = 0.018), the average difference of the VAS reached the minimal clinically important difference. No statistically significant difference in postoperative drug dosage of rescue analgesia, ROM, and complications. Preemptive analgesia combined with the early stage periarticular injection can better alleviate postoperative pain than the late stage periarticular injection.

Porous tantalum implant for treatment of early-stage osteonecrosis of the femoral head: a minimum 5-year follow-up study.

BACKGROUND: To evaluate the survival rate of porous tantalum rod implantation in the treatment of osteonecrosis of the femoral head (ONFH), evaluate its clinical effect and imaging results. METHODS: From January 2008 to December 2013, porous tantalum rod implantation for ONFH was performed in two institutions. Statistical analysis of operation data, including operation time, blood loss and blood transfusion were recorded. RESULTS: 52 hips received complete follow-up, the average follow-up time was 85.7 months (60-132 months). 24 hips turned to THA at the end of follow-up (46.2%), the average time was 44.3 ± 32.8 months, and the average Harris hip score before THA was 57.1 ± 7.6. Cox proportional-hazards model revealed that Association Research Circulation Osseous (ARCO) stage (P = 0.017), bone marrow edema (P = 0.006) and age > 40 years (P = 0.043) were independent risk factors for conversion to THA. CONCLUSION: ARCO stage, age and bone marrow edema were risk factors for the failure of porous tantalum rod implantation to convert to THA.

Comparison of outcomes between gap balancing and measured resection techniques for total knee arthroplasty: A prospective, randomized, controlled trial.

OBJECTIVE: The aim of this study was to compare the effect of Gap Balancing (GB) versus Measured Resection (MR) techniques on the early clinical and radiological results of Total Knee Arthroplasty (TKA). METHODS: In this prospective study, 99 patients (99 knees) who underwent unilateral TKA between March 2018 and January 2019 were randomly allocated to one of two groups: The GP group, TKA with GB technique (19 male, 31 female; mean age = 55.9 ±16.5) and the MR group, TKA with MR technique (19 male, 30 female; mean age = 54.2 ± 18.7). Patients in both groups were comparable in terms of the demographic and clinical data. The angle of cutting block to PCA and Cutting Thickness of the Medial and Lateral Condyle (CTMC, CTLC) were intraoperatively measured. In radiographic analysis, Preoperative Mechanical Femorotibial Angle (Pre-mFTA), Postoperative Mechanical Femorotibial Angle (Post-mFTA), and joint line changes were examined. Femoral component Rotation Angle (FCRA) was also measured by computed tomography. In gait analysis, the spatiotemporal parameters (walking speed, step length, and single support time) and kinematics parameters (flexion angle, extension angle, and transversal rotation) were collected at 12 months postoperatively. Furthermore, Western Ontario and McMaster Universities Arthritis Index (WOMAC) were performed at 12 months after surgery. RESULTS: CTMC and CTLC were both significantly higher in GB group than in the MR group (9.8±2.0 mm vs 8.5 ± 1.2 mm; 7.9 ± 1.8mm vs 6.8 ± 1.4mm; P = 0.001, P = 0.002, respectively). Angle of cutting block to PCA was statistically lower in GB group than in the MR group (1.7 ± 1.5° vs 3.1 ± 0.5 °; P < 0.001). FCRA is greater in the GB group compared to the MR group, but the difference did not reach statistical significance (1.2 ± 2.8 ° vs 0.7 ± 2.0 °; P > 0.05). Although post-mFTA significantly improved compared with pre-mFTA in both groups, no significant difference was observed in the changes of post-mFTA between the two groups (0.9 ± 1.7° vs 0.3 ± 1.8°, P > 0.05). No significant differences were determined between the two groups in spatiotemporal gait parameters including walking speed, step length, and single support time. The sagittal max knee flexion range was significantly larger in the GB group than in the MR group (49.27 ± 5.24 ° vs 45.99 ± 8.21 °, P < 0.05). The flexion range did not reach the level of the control group. There was no significant difference between the two groups in WOMAC at 12 months follow-up (P > 0.05). CONCLUSION: Evidence from this study has revealed GB and MR techniques have both little effect on early clinical results of TKA. Nonetheless, GB technique can provide better knee flexion in the early postoperative gait status compared with MR technique. LEVEL OF EVIDENCE: Level I, Therapeutic Study.

Cognitive behavioral therapy cannot relieve postoperative pain and improve joint function after total knee arthroplasty in patients aged 70 years and older.

PURPOSE: A randomized controlled trial was conducted to investigate whether cognitive behavioral therapy (CBT) can improve postoperative pain, knee function, and negative emotion in patients aged 70 years and older who underwent total knee arthroplasty (TKA). METHODS: This study used randomized, parallel group, controlled trial to divide the included 90 patients into CBT group and usual care group. The primary outcome measure of the study was the Visual Analogue Scale (VAS) at activity. The secondary outcome measures included the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Knee Range of Motion (ROM), Oxford Knee Score (OKS), Hospital for Special Surgery Knee Rating Scale (HSS), analgesics dose, and postoperative complications. RESULTS: 83 patients who met the criteria were randomized into CBT group and usual care group. In the SAS, score of the CBT group decreased by 4.3 points at 7th day and 8.2 at 14th day after surgery with respect to preoperative SAS score, the usual care group increased by 1.5 at 7th day and decreased 1.1 at 14th day, and tended to be similar at 3rd month after surgery. There were no significant differences at 7th and 14th day in SDS, however, score of the CBT group was 5.8 and the usual care group was 1.9 at 3rd month after surgery. No statistically significant differences in VAS at activity, ROM, OKS, HSS, analgesics frequency, and postoperative complications between two groups. CONCLUSIONS: CBT was superior to usual care group in relieving anxiety at 7th day and 14th day, and depression at 3rd month, however, CBT cannot relieve postoperative pain and improve joint function after TKA in patients aged 70 years and older.

[Construction of "2R network pharmacology" research method for effective components of traditional Chinese medicine based on "prediction of dominant components-screening of potential targets"].

Chinese traditional medicine compound is the main form of Chinese medicine clinical application. The elucidation of the effective components of traditional Chinese medicine is one of the key scientific issues to promote the modernization of traditional Chinese medicine. At present, there are many research ideas on the effective components of traditional Chinese medicine compounds. By analyzing the current status and existing problems of existing research ideas, the author proposes a "double reduction network pharmacology"(2 R network pharmacology) research method based on "prediction of dominant components-potential target selection". Chemical components with good properties were selected by ADMET property prediction technology, and compared with the blood components and target organ components to determine the dominant components with potential therapeutic effect, that is "reducing constituents"; the potential core regulatory pathway of traditional Chinese medicine compound was enriched by RNA-Seq technology combined with network database, and then the target of traditional Chinese medicine compound was mined based on the signal pathway, that is "reducing targets". To improve the efficiency and accuracy of effective component screening, the network relationship of "component target" was established by the related technology of network pharmacology. The purpose of this study is to provide practical research ideas and methods for clarifying the effective components of traditional Chinese medicine, revealing the law of compatibility of traditional Chinese medicine and clarifying the target of drug action.

Staged vs simultaneous bilateral unicompartmental knee arthroplasty for clinical outcomes: A protocol of systematic review and meta-analysis.

BACKGROUND: Bilateral unicompartmental knee arthroplasty (UKA) can be divided into one or two stages clinically. Compared with staged bilateral UKA, whether simultaneous bilateral UKA has better clinical efficacy remains to be verified. METHODS: PubMed, EBSCO, and Web of Science were searched by us for meta-analysis. Studies were considered eligible for inclusion if they included simultaneous and staged UKA. We excluded studies unrelated to the research question, studies in non-selected languages, and studies where the full-text was not available. The data were extracted by two independent investigators, and disagreements were resolved through discussions with a third party. If important data or information about the content of the paper were not available, authors were contacted. Publication bias in studies has been assessed. Meta-analysis was done using Review Manager 5.3. RESULTS: The systematic review and meta-analysis identified 3370 trials, of which 8 studies (963 patients) compared simultaneous with staged bilateral UKA. The meta-analysis showed that the clinical outcomes of simultaneous bilateral UKA goes down in operating time (weighted mean difference [WMD] = -19.34, 95% confidence interval [CI] -22.44 to -16.25, P < .00001), postoperative hemoglobin (Std. mean difference [SMD] = -0.46, 95% CI -0.71 to -0.20, P = .0004), length of stay (LOS) (WMD = -4.73, 95% CI -6.39 to -3.06, P < .00001), hospital cost (SMD = -5.42, 95% CI -6.54 to -4.30, P < .00001). There were no significant difference in blood transfusion, venous thrombosis, infection, cardiac complications, pulmonary complications, Oxford Knee Score (OKS) between simultaneous and staged bilateral UKA. CONCLUSION: Simultaneous bilateral UKA can effectively reduce the operating time, LOS, and hospital cost without increasing postoperative complications compared to stage bilateral UKA. REGISTRATION NUMBER: CRD42020160056 (www.crd.york.ac.uk/prospero/).

Deciphering the effective combinatorial components from Si-Miao-Yong-An decoction regarding the intervention on myocardial hypertrophy.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Miao-Yong-An decoction (SMYAD), a classical traditional Chinese medicine (TCM) formula, has been used to treat various cardiovascular diseases in clinics. AIM OF THE STUDY: The aim of this study is to investigate the effective combinatorial components from SMYAD and its mechanism regarding the intervention on myocardial hypertrophy. MATERIALS AND METHODS: SMYAD constituents absorbed in rat plasma and heart were identified using UHPLC Q-Exactive-Orbitrap MS/MS. The identified constituents in SMYAD were further analyzed using ADMET (absorption, distribution, metabolism, excretion and toxicity) prediction and molecular docking. The effective constituents were identified using isoproterenol (ISO)-induced H9c2 cardiomyocyte hypertrophy, and neochlorogenic acid (NCA), chlorogenic acid (CA), cryptochlorogenic acid (CCA), isochlorogenic acid C (ICAC), angoroside C (AGDC), isochlorogenic acid A (ICAA), sweroside (SRD), and harpagide (HPD) in SMYAD extract were quantified by HPLC for compatibility. Finally, anti-hypertrophic activities of candidate effective combinatorial components, which were prepared according to the determined molar concentration ratio of effective constituents using reference substance solution, were analyzed using immunofluorescence staining and Quantitative real-time PCR. The expression levels of PI3Kα, p-ERK, p-Akt, Akt, p-mTOR, mTOR and HIF-1α were measured using Western blot. RESULTS: 32 prototypes of SMYAD were identified from plasma and heart tissue of rat. Combining with ADMET prediction, 31 dominant constituents were focused. Based on HIF-1 pathway identified in preliminary result, 17 targets were focused, which were used to dock with 31 constituents. 27 constituents were therefore hit as the potential effective constituents of SMYAD in inhibiting myocardial hypertrophy. Bioactivity evaluation showed that NCA, CA, CCA, ICAC, AGDC, ICAA, SRD, and HPD significantly inhibited the increase of H9c2 cell surface area induced by ISO. Except for ICAA and AGDC, the remaining 6 effective constituents, showing a certain inhibitory effect on ISO-induced ANP mRNA overexpression at high and low concentrations, participated in compatibility based on the molar concentration ratio determined by HPLC. Effective combinatorial components composed of the 6 effective constituents (effective combinatorial components ABC) showed significant inhibitory effect on the increase of cell surface area, and the overexpression of ANP and ß-MHC mRNA in H9c2 cells induced by ISO. Moreover, effective combinatorial components ABC significantly inhibited the protein overexpressions of p-Akt, p-mTOR and HIF-1α. Based on the results, we put forward the strategy of "Focusing constituents" and "Focusing targets" for the effective constituents research of TCM formula. CONCLUSION: Effective combinatorial components ABC composed of NCA, CA, CCA, ICAC, SRD and HPD from SMYAD inhibited ISO-induced cardiomyocyte hypertrophy and down-regulated expression of ANP and ß-MHC mRNA through the inactivation of Akt/mTOR/HIF-1α pathway.

Radiotherapy for the prophylaxis of heterotopic ossification after total hip arthroplasty: A systematic review and meta-analysis of randomized controlled trails.

Heterotopic ossification (HO) refers to the formation of lamellar bone in soft tissues and is a significant complication after total hip arthroplasty (THA). Radiotherapy has been proven as an effective prophylaxis especially for those patients with high risk of HO after THA. However the dose, timing, and frequency of radiation have yet to be determined. To compare HO progressions with different radiotherapy strategies and explore an optimal radiation option. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trails (through December 1, 2019; no language restrictions) collecting patients who accepted prophylaxis radiation for whom HO progression outcomes were reported. Of 87 identified studies, 10 randomized controlled trails including 1203 patients and 1268 hips were taken to this analysis. Compared with the low biologically effective radiation dose group (biologically effective dose [BED] < 20 Gy), the medium biologically effective radiation dose group (20 Gy ≤ BED ≤ 24 Gy) had statistically significant difference on the prophylaxis of HO (p = 0.003). But for overall incidence of HO, there was no statistically significant difference between low BED group and high BED group (BED > 24, p = 0.21). There was statistically significant reduction in the prophylaxis of HO progression with multiple fractions as opposed to single fraction radiotherapy (p = 0.04). Hips with preoperative radiation were no more likely to observe HO progression than those with postoperative radiotherapy (p = 0.43). Radiotherapy with medium dose (20 Gy ≤ BED ≤ 24 Gy) after THA is an effective dose for preventing HO. In the prophylaxis of HO, multiple fractions seem to be more effective than single fraction radiation. Preoperative radiotherapy could prevent HO progression with the same efficacy postoperative.

Mid- and long-term efficacy of surgical treatment of Vancouver B2 and B3 periprosthetic femoral fractures.

BACKGROUND: The incidence of fractures around the femoral prosthesis among patients undergoing hip arthroplasty is increasing and has become the third leading cause of hip revision. While numerous methods for the surgical treatment of periprosthetic femoral fractures (PFFs) have been proposed, only few reports have examined the long-term efficacy of surgical treatment. This study aims to examine the mid-and long-term efficacy of surgical treatment among patients with Vancouver B2 and B3 PFFs. METHODS: This retrospective study evaluated the surgical outcomes of patients with Vancouver B2 and B3 PFFs between 2007 and 2011. The minimum follow-up time was eight years. Fracture healing, prosthesis stability, complications, patient quality of life SF-36 score, and survival rate were evaluated during the follow-up assessments. RESULTS: A total of 83 patients were included and had an average follow-up period of 120.3 months. Among these patients, 69 were classified as Vancouver B2 and were treated with a distal fixation stem, whereas 14 cases were classified as Vancouver B3 and were treated with modular femoral prosthesis by using a proximal femoral allograft technique. A total of 15 patients underwent secondary revision surgery, and prosthesis dislocation was identified as the main cause of secondary revision. 80 (96.4%) cases of fractures were clinically healed. The mortality rate in the first year after surgery was 8.4% (7/83). The overall 5-year Kaplan-Meier survival rate for these patients was 75.9%. Meanwhile, the 5-year Kaplan-Meier survival rate for the implants was 86.9%. The final follow-up SF-36 score of the patients was 48.3 ± 9.8. CONCLUSIONS: Patients with Vancouver B2 and B3 PFFs show high mortality in the first year after their surgery, and the Kaplan-Meier analysis results showed that such mortality tends to plateau after 5 years. Prosthesis dislocation was identified as the primary cause of secondary revision.

Correction to: Direct anterior versus posterolateral approaches for clinical outcomes after total hip arthroplasty: a systematic review and meta-analysis.

An amendment to this paper has been published and can be accessed via the original article.

Advantages of 16S rRNA PCR for the diagnosis of prosthetic joint infection.

16S ribosomal RNA (rRNA) PCR has been reported to be an effective diagnostic means in patients with prosthetic joint infection (PJI). The aim of the present meta-analysis is to establish the overall diagnostic accuracy of the measurement of 16S rRNA PCR for diagnosing PJI. PubMed, Web of Science, Cochrane Library, EMBASE and Wiley Online Library were searched for studies on 16S rRNA PCR in the diagnosis of PJI. The search incorporated all literature published up until December 2018 and the QUADAS-2 checklist were used for quality assessment. The sensitivity, specificity and other measures of accuracy of 16S rRNA PCR in the diagnosis of PJI were pooled. Statistical analysis was performed by employing Meta-Disc 1.4 and Stata 12.0 software. A total of 15 studies met the inclusion criteria. The summary estimates for 16S rRNA PCR in the diagnosis of PJI in these studies were pooled: Sensitivity, 0.70 (95% CI, 0.67-0.73); specificity, 0.93 (95% CI, 0.91-0.94); positive likelihood ratio, 10.93 (95% CI, 5.55-21.51); negative likelihood ratio, 0.33 (95% CI, 0.28-0.40); diagnostic odds ratio, 41.77 (95% CI, 19.90-87.68); and the area under the curve, 0.89. Subgroup analysis showed that the use of sonicate fluid and periprosthetic tissue has higher sensitivity (0.76; 95% CI, 0.69-0.82; and 0.73; 95% CI, 0.68-0.78, respectively), specificity (0.93, 95% CI, 0.90-0.96; and 0.95; 95% CI, 0.90-0.98, respectively) and area under the curve (0.93 and 0.98, respectively). 16S rRNA PCR assay plays an important role in the diagnosis of PJI. The results of 16S rRNA PCR assays should be interpreted in parallel with clinical findings, the results of microbiological, and other laboratory tests.

Comparison of modular and nonmodular tapered fluted titanium stems in femoral revision hip arthroplasty: a minimum 6-year follow-up study.

Both modular and nonmodular tapered fluted titanium stems are commonly used in revision total hip arthroplasty (THA). However, which type of femoral stem is superior remains controversial. The purpose of this study was to assess the clinical and radiographic outcomes of modular and nonmodular tapered fluted titanium. The clinical data of patients undergoing primary revision THA from January 2009 to January 2013 in two institutions were retrospectively analyzed. According to the type of prosthesis used on the femoral side, the patients were divided into the modular group (108 hips; Link MP modular stem in 73 hips and AK-MR modular stem in 35 hips) and nonmodular group (110 hips; Wagner SL stem in 78 hips and AK-SL stem in 32 hips). The operative time, hospital stay, blood loss, blood transfusion volume, hip function, hip pain, limb length discrepancy, imaging data, and complications were compared between the two groups.A total of 218 patients were followed up for 78-124 months, with an average of 101.5 months. The incidence of intraoperative fracture in the modular group (16.7%) was significantly higher than that in the nonmodular group (4.5%; (P < 0.05). At the last follow-up, the limb length difference in the modular group (2.3 ± 2.7 mm) was significantly lower than that in the nonmodular group (5.6 ± 3.5 mm; P < 0.05), and the postoperative prosthesis subsidence in the modular group (averaged 0.92 mm; 0-10.2 mm) was significantly less than that in the nonmodular group (averaged 2.20 mm; 0-14.7 mm; P < 0.05). Both modular and nonmodular tapered fluted titanium stems can achieve satisfactory mid-term clinical and imaging results in patients who underwent femoral revision. The modular stems have good control of lower limb length and low incidence of prosthesis subsidence.