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Background: Cerebral ischemia/reperfusion (I/R) injury is a serious vascular disease with extremely high mortality and disability rate. Bakuchiol (BAK) was found in leaves and seeds of Psoralea corylifolia Linn and has been shown to decrease inflammation and reduce oxidative stress, while the mechanism of BAK in ameliorating cerebral I/R injury remains unclear., Methods: Middle cerebral artery occlusion reperfusion (MACO/R) was used to establish mouse model. The protective effect of BAK in MCAO/R mices was detected by performing neurological deficit testing, TTC staining, and H&E staining. Oxygen/glucose deprivation and reperfusion (OGD/R) was used to stimulate SH-SY5Y cells in vitro. Protein expression was detected by western blotting, gene expression was detected by quantitative real-time polymerase chain reaction and apoptosis was detected by immunofluorescence., Results: Our study indicated that BAK protected ischemia-reperfusion injury in MACO/R mice, and upregulated superoxide dismutase (SOD) and the catalase (CAT) enzyme activity. BAK also inhibited the expression of TNF-α, IL-1β, IL-6, and IL-18 and suppressed apoptosis and pyroptosis both in MACO/R mice and in OGD/R SH-SY5Y cells. Further results showed that BAK could suppress TXNIP, ASC, NLRP3, and caspase-1 mRNA levels to reverse assembly of inflammasome. And BAK could also upregulate the expression of phosphorylated AMP-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor (Nrf2). In addition, Nrf2 inhibitor ML385 reversed the BAK induced reduction of TXNIP, ASC, NLRP3, and the AMPK inhibitor also abolished BAK' the effect on the regulation of Nrf2, TXNIP, ASC, NLRP3, caspase-1, and pro-inflammatory cytokines. In conclusion, BAK, found in leaves and seeds of Psoralea corylifolia Linn, could ameliorated cerebral I/R injury through activating AMPK/Nrf2 to inhibit NLRP3 inflammasome, which might present new therapeutic strategy for cerebral I/R injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The clinical interpretation of patient-reported outcome measures (PROMs) after anterior cruciate ligament (ACL) reconstruction (ACLR) can be challenging. This study aimed to establish the clinical relevance of PROMs by determining maximal outcome improvement (MOI) thresholds at mid-term follow-up after primary ACLR., Methods: A total of 343 patients who underwent primary single-bundle ACLR using hamstring tendon autograft at our institute were included. Patients were queried with a 2-option anchor question regarding satisfaction with their current knee symptom state. The MOI of a PROM was calculated for each patient as the percentage of improvement normalized by the maximal possible improvement. The MOI threshold for each PROM was determined as the optimal cutoff value for predicting patient satisfaction based on receiver operating characteristic curve analysis. Multivariable logistic regression analyses were performed to identify predictors of achieving these thresholds. Subgroup analyses that stratified the time from injury to surgery within the cohort were performed, and MOI thresholds were recalculated within each of these subgroups. The PROMs evaluated in this study were the modified Lysholm Knee Score and the International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC) score., Results: The calculated MOI threshold was 35.1% for the Lysholm score and 46.7% for the IKDC score. A longer time from injury to surgery reduced the odds of achieving the MOI threshold for the Lysholm score (odds ratio [OR] per time bracket = 0.7114, p < 0.0001) and IKDC score (OR = 0.8038, p = 0.0003). Male sex was associated with higher odds of achieving the MOI threshold for the IKDC score (OR = 1.9645, p = 0.0143). For patients with chronicity of ≤6 months, the MOI threshold was 35.1% for the Lysholm score and 57.9% for the IKDC score, and for patients with chronicity of >6 months, the thresholds were 24.5% and 27.1%, respectively., Conclusions: The calculated MOI thresholds for the Lysholm and IKDC scores at mid-term follow-up after primary ACLR were 35.1% and 46.7%, respectively. Greater chronicity of the ACL injury was associated with lower odds of achieving the MOI thresholds for the PROMs at mid-term follow-up., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: This study was supported by the Clinical Cohort Project Program of Peking University Third Hospital (BYSYDL2021014, BYSYDL2023018). The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/I270)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Cyclic carbonate hydrogenation offers an alternative for the efficient indirect CO 2 utilization. In this study, a series of carbon nanotubes (CNTs) supported xCu/CNTs catalysts with different Cu loadings were fabricated using a convenient impregnation method, and exhibited excellent catalytic activity for the hydrogenation of ethylene carbonate to methanol and ethylene glycol. The structural and physicochemical properties revealed that acid treatment of CNTs resulted in plentiful oxygen-containing functional groups, providing sufficient anchoring sites for copper species. The calcination process conducted under an inert atmosphere resulted in the formation of ternary CuO, Cu 2 O, and Cu composites, enhancing the metal-support interaction and facilitating the formation of balanced Cu 0 and Cu + dual sites as well as high active surface area after reduction. Contributed to the synergetic effect of balanced Cu + and Cu 0 species proved by density functional theory calculation and the electron-rich CNTs surface, the 40Cu/CNTs catalyst achieved strengthened catalytic performance with methanol yield of 83 %, ethylene glycol yield of 99 % at ethylene carbonate conversion of >99 %, and 150 h of long-term running stability. Consequently, CNTs supported Cu serve as efficient non-silica based catalyst for ester hydrogenation., (© 2024 Wiley-VCH GmbH.)

Utilizing spontaneous polarization field to harness charge transfer kinetics is a promising strategy to boost photocatalytic performance. Herein, a novel Cu atom clusters/PtCu alloy nanocubes coloaded on nitrogen-rich triazole-based C 3 N 5 (PtCu-C 3 N 5 ) with dipole field was constructed through facile photo-deposition and impregnation method. The dipole field-drive spontaneous polarization in C 3 N 5 acts as a charge-transfer bridge to promote directional electron migration from C 3 N 5 to Cu atom clusters/PtCu alloy. Through the synergistic effects between Cu atom clusters, PtCu alloy and dipole field in C 3 N 5 , the optimized Pt 2 Cu 3 -C 3 N 5 achieved a record-high performance with H 2 formation rate of 4090.4 μmol g -1  h -1 under visible light, about 154.4-fold increase compared with pristine C 3 N 5 (26.5 μmol g -1  h -1 ). Moreover, the apparent quantum efficiency was up to 25.33 % at 320 nm, which is greatly superior than most previous related-works. The directional charge transfer mechanism was analyzed in detail through various characterizations and DFT calculations. This work offers a novel pathway to construct high-efficiency multi-metal photocatalysts for solar energy conversion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

As a typical perovskite material, NaTaO 3 has been regarded as a potential catalyst for photocatalytic hydrogen evolution (PHE) process, due to its excellent photoelectric property and superior chemical stability. However, the photocatalytic activity of pure NaTaO 3 was largely restricted by its poor visible-light absorption ability and rapid recombination of photogenerated charge carriers. Therefore, a covalently bonded TpBpy covalent organic framework (COF)/NaTaO 3 (TpBpy/NaTaO 3 ) heterostructure was designed and synthesized by the post modification strategy with (3-aminopropyl) triethoxysilane (APTES) and the in situ solvothermal process. Benefiting from the enhanced built-in electric field by the interfacial covalent bonds and the formation of S-scheme heterostructure between TpBpy and NaTaO 3 , which were proved by the Ar + -cluster depth profile and X-ray photoelectron spectroscopy (XPS), as well as density functional theory (DFT) calculation results, both the charge transfer efficiency and the PHE performance of the TpBpy/NaTaO 3 composites were significantly improved. Additionally, the composites exhibited an excellent absorption performance in the visible region, which was also beneficial for the photocatalytic process. As expected, the optimal TpBpy/20%NaTaO 3 composite achieved a remarkable hydrogen evolution rate of 17.3 mmol·g -1 ·h -1 (10 mg of catalyst) under simulated sunlight irradiation, which was about 173 and 2.4 times higher than that of pure NaTaO 3 and TpBpy, respectively. This work provided a novel strategy for constructing highly effective and stable semiconductor/COFs heterostructures with strong interfacial interaction for photocatalytic hydrogen evolution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Corydalis Rhizome (RC) as a traditional analgesic Chinese medicine is the dried tuber of Corydalis yanhusuo W.T.Wang. Many efforts have revealed that RC could effectively alleviate neuropathic pain, while its active ingredients in neuropathic pain are still not clear., Aim of the Study: Spinal central sensitization contributes greatly to neuropathic pain, and neuron, astrocyte and microglia play important roles in spinal central sensitization. The aim of the present study is to excavate active compounds in RC regulating spinal central sensitization to inhibit neuropathic pain., Materials and Methods: Immunofluorescence and western blotting were used to determine protein expression levels. Gene expression levels were detected by RT-PCR. PC12 neuronal cells, C6 astrocyte cells, and BV2 microglia cells were cultured for in vitro studies. Targeting multi types of cells extraction combined with HPLC-Q-TOF-MS/MS was established to identify components binding to above cells. Animal studies were used to verify the analgesic activities of components., Results: Total alkaloids of RC (RC-TA) significantly relieved neuropathic pain in chronic constriction injury (CCI) rats and repressed spinal central sensitization. Eight components of RC-TA were found to bind to PC12, C6, or BV2 cells. They could respectively suppress the activation of cells in vitro and alleviate CCI-induced neuropathic pain, among which glaucine and dehydrocorydaline induced antinociception was stronger than l-THP. Meanwhile, glaucine had no effect on acute or chronic inflammatory pain, and its antinociception in neuropathic pain could be abolished by dopamine D1 receptor agonist., Conclusions: Employing multi types of cells based on spinal central sensitization rather than single cell may allow for more thorough excavation of active substances. Glaucine was firstly found could attenuate neuropathic pain but not other types of pain which indicated that different alkaloids in RC exert distinct analgesic effects on different pain models, and gluacine has the potential to be developed as an analgesic drug specifically for neuropathic pain relieving., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Dopamine receptors have been reported to be involved in pain, while the exact effects and mechanism in bone cancer pain have not been fully explored. Methods: Bone cancer pain model was created by implanting walker 256 mammary gland carcinoma into right tibia bone cavity. Primary cultured spinal neurons were used for in vitro evaluation. FLIPR, western-blot, immunofluorescence, and Co-IP were used to detect cell signaling pathway. Results: Our results indicated that spinal dopamine D1 receptor (D1DR) and spinal dopamine D2 receptor (D2DR) could form heteromers in TCI rats, and antagonizing spinal D1DR and D2DR reduced heteromers formation and alleviated TCI-induced bone cancer pain. Further results indicated that D1DR or D2DR antagonist induced antinociception in TCI rats could be reversed by D1DR, D2DR, and D1/D2DR heteromer agonists. And Gq, IP3, and PLC inhibitors also attenuated TCI-induced bone cancer pain. In vitro results indicated that D1DR or D2DR antagonist decreased the Ca 2+ oscillations upregulated by D1DR, D2DR, and D1/D2DR heteromer agonists in activated primary cultured spinal neurons. Moreover, inhibition of D1/D2DR heteromers induced antinociception in TCI rats was partially mediated by the CaMKII and MAPKs pathway. In addition, a natural compound levo -Corydalmine ( l- CDL), could inhibit D1/D2DR heteromers and attenuate bone cancer pain. Results: Inhibition of spinal D1/D2DR heteromers via l- CDL decreases excitability in spinal neurons, which might present new therapeutic strategy for bone cancer pain., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients., Methods: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE., Results: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants., Conclusions: In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients., (© 2023 JGC All rights reserved; www.jgc301.com.)

Background: Due to the anatomically adjacent relationship between the left atrium (LA) and esophagus, energy delivery on the posterior wall of LA is limited. The aim of this study was to evaluate the feasibility of a novel esophageal retractor (SAFER) with an inflatable C-curve balloon during atrial fibrillation (AF) ablation., Method: Nine patients underwent AF ablation assisted with the SAFER. After inflation, the esophagus was deviated laterally away from the intended ablation site of the posterior wall under local anesthesia. The extent of mechanical esophageal deviation (MED) was evaluated under fluoroscopy, defined as the shortest distance from the trailing esophageal edge to the closest point of the ablation line. Gastroscopy was performed before and after ablation. The target ablation index used in all LA sites including the posterior wall was 400-450 after effective MED. All adverse events during the periprocedural period were recorded., Results: The mean deviation distance achieved 16.2 ± 9.6 mm away from the closest ablation point of the pulmonary vein lesion set. With respect to the individual left and right pulmonary vein lesion sets, the deviation distance was 19.7 ± 11.5 and 12.7 ± 6.8 mm, respectively. The extent of deviation was 0 to 5 mm, 5.1 to 10 mm, or >10 mm in 0(0%), 7(38.9%), and 11(61.1%), respectively. Procedural success was achieved in all patients without acute reconnection. There was only one esophageal complication which manifested as esophageal erosion and this patient experienced throat pain possibly related to the SAFER retractor with no clinical sequelae., Conclusion: Esophageal deviation with the novel eccentric balloon is a novel feasible choice during AF ablation, enabling adequate energy delivery to the posterior wall of LA. Additional prospective randomized controlled studies are required for further validation., (© 2023 Wiley Periodicals LLC.)

The construction of heterojunctions is commonly regarded as an efficient way to promote the production of hydrogen via photocatalytic water splitting through the enhancement of interfacial interactions. The p-n heterojunction is an important kind of heterojunction with an inner electric field based on the different properties of semiconductors. In this work, we reported the synthesis of a novel CuS/NaNbO 3 p-n heterojunction by depositing CuS nanoparticles on the external surface of NaNbO 3 nanorods, using a facile calcination and hydrothermal method. Through the screening of different ratios, the optimum hydrogen production activity reached 1603 μmol·g -1 ·h -1 , which is much higher than that of NaNbO 3 (3.6 times) and CuS (2.7 times). Subsequent characterizations proved semiconductor properties and the existence of p-n heterojunction interactions between the two materials, which inhibited the recombination of photogenerated carriers and improved the efficiency of electron transfer. This work provides a meaningful strategy to utilize the p-n heterojunction structure for the promotion of photocatalytic hydrogen production., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To study the safety and electrical characteristics of various implanting sites of the Micra pacemaker., Method: A total of 15 patients from Beijing Anzhen Hospital, Capital Medical University, were included, who were implanted with Micra leadless pacemakers and allocated to either the high ventricular septum group (eight patients) or the low ventricular septum group (seven patients) based on their individual patient factors and clinical conditions. The baseline of the patients, the implanting area, the electrocardiogram change after implantation, the implantation data, the threshold, R wave, impedance, and the date of the 1-month follow-up were then analyzed. With all of the data, the characteristics of different implantation sites of the Micra pacemaker were determined., Results: Overall, the thresholds were low at implantation and remained stable over the 1-, 3-, 6-month, 1-, 2-, 3-, and 4-year follow-ups. On comparing the two groups, there was no difference in QRS duration at pacing (140.00 [40.00] ms vs. 179.00 [50.00] ms), threshold at implantation (0.38 [0.22] mV vs. 0.63 [1.00] mV), R wave at implantation ([10.85 ± 4.71] V vs. [7.26 ± 2.98] V), or impedance at implantation ([906.25 ± 162.39] Ω vs. [750.00 ± 173.40] Ω). While the difference in QRS duration between the two groups was not significant, the QRS duration of the high ventricular septum group exhibited a reduced tendency compared with that of the low ventricular group. The corrected QT interval during pacing exhibited a significant difference (440.00 [80.00] ms vs. 520.00 [100.00] ms; p < .05). For the 1-, 3-, 6-month, 1-, 2-, 3-, and 4-year follow-ups, there was no difference between the threshold of the high ventricular septum group and that of the low ventricular septum group (p > .05)., Conclusion: High ventricular septum pacing appears to be a safe site for implantation of the Micra pacemaker. It could entail a shorter QRS duration at pacing and could be more physiological than low ventricular septum pacing., (© 2023 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Background: Congenitally corrected transposition of the great arteries (ccTGA) is a rare cardiac anomaly and can lead to abnormal electrical activity of the heart. The implant of a pacemaker in such patients is more complicated than conventional operations. This case report of an adult with ccTGA who had a leadless pacemaker implant will provide a reference for diagnosing and treating such patients., Case Presentation: A 50-year-old male patient was admitted to hospital having experienced intermittent vision loss for a month. An electrocardiogram and Holter monitoring showed intermittent third-degree atrioventricular block, and echocardiography, cardiac computed tomography and cardiac magnetic resonance imaging confirmed a diagnosis of ccTGA. A leadless pacemaker was successfully implanted into the patient's anatomical left ventricle, and the postoperative parameters were stable., Conclusion: Implanting a leadless pacemaker into a patient with a rare anatomical and electrophysiological abnormality, such as ccTGA, is feasible and efficacious, but preoperative imaging evaluation is of considerable importance., (© 2023. The Author(s).)

Aims: Fascicular ventricle tachycardia (FVT) arising from the proximal aspect of left His-Purkinje system (HPS) has not been specially addressed. Current study was to investigate its clinical, electrocardiographic, and electrophysiological characteristics., Methods and Results: Eighteen patients who were identified as this rare FVT were consecutively enrolled, and their scalar electrocardiogram and electrophysiological data were collected and analysed. The ventricular tachycardia (VT) morphology was similar to sinus rhythm (SR) in eight patients, left bundle branch block type in one patient, right bundle branch block type in seven patients, and both narrow and wide QRS type in two patients. During VT, right-sided His potential preceded the QRS with His-ventricle (H-V) interval of 36.3 ± 12.4 ms, which was shorter than that during SR (-51.4 ± 8.6 ms) (P = 0.002). The earliest Purkinje potentials (PPs) were recorded within 7 ± 3 mm of left-side His and preceded the QRS by 49.1 ± 14.0 ms. Mapping along the left anterior fascicle and left posterior fascicle revealed an antegrade activation sequence in all with no P1 potentials recorded. In the two patients with two VT morphologies, the earliest PP was documented at the same site, and the activation sequence of HPS remained antegrade. Ablation at the earliest PP successfully eliminated the tachycardia, except one patient who developed complete atrial-ventricular block and two patients who abandoned ablations. After at least 12 months follow-up, 15 patients were free from any recurrences., Conclusions: Fascicular ventricle tachycardia arising from the proximal aspect of left HPS was featured by recording slightly shorter H-V interval and absence of P1 potentials. Termination of VT requires ablation at the left-sided His or its adjacent region., Competing Interests: Conflict of interest : None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To investigate the timing of pericardial drainage catheter removal and restart of the anticoagulation in patients with atrial fibrillation (AF) suffered from perioperative pericardial tamponade during atrial fibrillation catheter ablation and uninterrupted dabigatran. Methods: A total of 20 patients with pericardial tamponade, who underwent AF catheter ablation with uninterrupted dabigatran in Beijing Anzhen Hospital from January 2019 to August 2021, were included in this retrospective analysis. The clinical characteristics of enrolled patients, information of catheter ablation procedures, pericardial tamponade management, perioperative complications, the timing of pericardial drainage catheter removal and restart of anticoagulation were analyzed. Results: All patients underwent pericardiocentesis and pericardial effusion drainage was successful in all patients. The average drainage volume was (427.8±527.4) ml. Seven cases were treated with idarucizumab, of which 1 patient received surgical repair. The average timing of pericardial drainage catheter removal and restart of anticoagulation in 19 patients without surgical repair was (1.4±0.7) and (0.8±0.4) days, respectively. No new bleeding, embolism and death were reported during hospitalization and within 30 days following hospital discharge. Time of removal of pericardial drainage catheter, restart of anticoagulation and hospital stay were similar between patients treated with idarucizumab or not. Conclusion: It is safe and reasonable to remove pericardial drainage catheter and restart anticoagulation as soon as possible during catheter ablation of atrial fibrillation with uninterrupted dabigatran independent of the idarucizumab use or not in case of confirmed hemostasis.

Designing Step-scheme (S-scheme) heterojunction with the directional charge transfer pathway has been considered as a promising strategy for realizing effective spatial separation of photo-generated carriers in a photocatalytic system by utilizing broadband solar energy. Herein, the novel and ternary S-scheme heterojunction photocatalysts were fabricated by embedding Au nanoparticles (NPs) on the surface of ZnIn 2 S 4 /NaTaO 3 composites through a facile two-step hydrothermal method for the first time. As expected, it showed an enhanced hydrogen evolution rate of 11404 μmol g -1  h -1 , which was approximately 58 and 10 times higher than that of the pristine NaTaO 3 nanocubes (197 μmol g -1  h -1 ) and ZnIn 2 S 4 microspheres (1180 μmol g -1  h -1 ) under simulated sunlight irradiation, respectively. An intimate heterojunction interface as well as Au nanoparticles as electron reservoir and reactive sites, which enhanced light absorption capacity and accelerated charge carrier separation, was answerable to the huge promotion in the photocatalytic performance. Most notably, XPS, EPR analysis and density functional theory (DFT) calculation results, revealed that the presence of strong interfacial electric fields promoted superior separation efficiency in the Au-ZnIn 2 S 4 /NaTaO 3 S-scheme heterojunction. This innovative work may shed light on a more appealing and meaningful approach to modify sodium tantalate for the promising application in photocatalytic hydrogen generation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Enhancing the interfacial charge carriers transfer efficiency is important for designing photocatalysts with excellent hydrogen evolution performance. In this work, we have successfully constructed a In 2 O 3 @InN/ZnIn 2 S 4 ternary heterostructure by embedding InN at the interface of thin-layered ZnIn 2 S 4 and tubular In 2 O 3 derived from metal-organic frameworks (MOFs) nanorods for the first time. The InN can not only adjust the energy band structure of In 2 O 3 , but also boost the photogenerated charge carriers transfer at the interface of In 2 O 3 and ZnIn 2 S 4 . The optimum photocatalytic hydrogen evolution rate of In 2 O 3 @InN/ZnIn 2 S 4 composite reaches 275 µmol/h (50 mg of catalyst) under simulated sunlight irradiation, which is obviously higher than pure In 2 O 3 (12.5 times), ZnIn 2 S 4 (2.5 times) and binary In 2 O 3 /ZnIn 2 S 4 (1.8 times) photocatalysts. This work can offer a meaningful strategy to promote the interfacial charge separation in the heterostructure for excellent photocatalytic hydrogen evolution activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The hydrogenation of CO 2 -derived carbonates to methanol is an alternative route for the indirect utilization of abundant C1 sources. Various Cu/SiO 2 catalysts with different copper loading content prepared by using an ammonia evaporation hydrothermal method are implemented to evaluate the catalytic performance of ethylene carbonate (EC) hydrogenation to methanol and ethylene glycol (EG). The Cu loading content was identified to significantly affect the Cu nanoparticles (NPs) size and metal-support interaction. Highly dispersed Cu NPs restricted and embedded in copper phyllosilicate presented a smaller average particle size than the impregnated Cu/SiO 2 -IM catalyst. The x Cu/SiO 2 catalyst with ultrafine Cu NPs showed abundant Cu-O-Si interfaces, acidic sites, and coherent Cu 0 and Cu + species. The 5Cu/SiO 2 catalyst achieved methanol yield of 76% and EG yield of 98% at EC conversion of 99%, and no obvious deactivation was observed after long-term operation. The superior catalytic performance of the 5Cu/SiO 2 catalyst is attributed to the synergetic effect between the appropriate Cu 0 surface area which provides sufficient active hydrogen, and the atomic ratio of Cu + for the polarization and activation of carbon-oxygen bonds., (© 2022 IOP Publishing Ltd.)

Purpose: This study aimed to evaluate the diagnostic performance of convolutional neural network (CNN) models in Chiari malformation type I (CMI) and to verify whether CNNs can identify the morphological features of the craniocervical junction region between patients with CMI and healthy controls (HCs). To date, numerous indicators based on manual measurements are used for the diagnosis of CMI. However, the corresponding postoperative efficacy and prognostic evaluations have remained inconsistent. From a diagnostic perspective, CNN models may be used to explore the relationship between the clinical features and image morphological parameters., Methods: This study included a total of 148 patients diagnosed with CMI at our institution and 205 HCs were included. T1-weighted sagittal magnetic resonance imaging (MRI) images were used for the analysis. A total of 220 and 355 slices were acquired from 98 patients with CMI and 155 HCs, respectively, to train and validate the CNN models. In addition, median sagittal images obtained from 50 patients with CMI and 50 HCs were selected to test the models. We applied original cervical MRI images (CI) and images of posterior cranial fossa and craniocervical junction area (CVI) to train the CI- and CVI-based CNN models. Transfer learning and data augmentation were used for model construction and each model was retrained 10 times., Results: Both the CI- and CVI-based CNN models achieved high diagnostic accuracy. In the validation dataset, the models had diagnostic accuracy of 100% and 97% (p = 0.005), sensitivity of 100% and 98% (p = 0.016), and specificity of 100% (p = 0.929), respectively. In the test dataset, the accuracy was 97% and 96% (p = 0.25), sensitivity was 97% and 92% (p = 0.109), and specificity was 100% (p = 0.123), respectively. For patients with cerebellar subungual herniation less than 5 mm, three out of the 10 CVI-based retrained models reached 100% sensitivity., Conclusions: Our results revealed that the CNN models demonstrated excellent diagnostic performance for CMI. The models had higher sensitivity than the application of cerebellar tonsillar herniation alone and could identify features in the posterior cranial fossa and craniocervical junction area of patients. Our preliminary experiments provided a feasible method for the diagnosis and study of CMI using CNN models. However, further studies are needed to identify the morphologic characteristics of patients with different clinical outcomes, as well as patients who may benefit from surgery., (Copyright © 2022. Published by Elsevier B.V.)

Generally, an excellent cocatalyst could promote the photocatalytic hydrogen (H 2 ) evolution performance of g-C 3 N 4 significantly. Herein, a superior cocatalyst of gold-platinum (AuPt) nanocrystal with an ultralow content of Pt was successfully decorated on carbon self-doping g-C 3 N 4 nanosheets (AuPt/CCN) via a facile photodeposition route. The corresponding Pt/CCN, Au/CCN, Au/Pt/CCN, and Pt/Au/CCN were also prepared for comparison. It is found that AuPt/CCN exhibits much superior photocatalytic H 2 evolution performance (1135 μmol/h) when irradiated with a 300 W Xe lamp, up to 20, 12, 5, 2, and 1.5 times that of the pristine CCN, Pt/CCN, Au/CCN, Au/Pt/CCN, and Pt/Au/CCN, respectively. The quantum efficiency (QE) of AuPt/CCN at 420 nm reaches 12.5%. The experimental and density functional theory calculation results suggested that the improved AuPt performance can be mainly ascribed to the non-plasmon-related synergistic effect of Au and Pt atoms in AuPt nanocrystal: (1) the proximity and the electronegativity difference of Au and Pt atoms in AuPt accelerate the transfer and separation of charge carriers and (2) the synergistic interaction between Pt and Au atoms optimizes the Gibbs free energy (Δ G H* ) of H* (atom) adsorption on AuPt, promoting the H 2 generation kinetics of AuPt/CCN.

Objective: To evaluate the safety and effectiveness of left atrial appendage occlusion (LAAO) in patients with atrial fibrillation and end-stage renal disease undergoing long-term hemodialysis. Methods: Six patients with AF and end-stage renal disease(ESRD)on long term hemodialysis who underwent LAAO from March 2017 to March 2021 in Beijing Anzhen Hospital were enrolled. Baseline characteristics such as age, sex, types of arrhythmia, stroke and bleeding score, and continuous dialysis time were collected. Four patients underwent LAAO, two patients underwent the combined procedure of catheter ablation and LAAO. Perioperative treatment and serious complications were recorded. Transesophageal echocardiography was repeated at 45 days and 60 days after the procedure. Telephone follow-up was conducted at 3, 6 and 12 months after the procedure, and every 6 months thereafter. Thromboembolism and major bleeding events and survival were evaluated. Results: The average age was (66.7±17.0) years old, and 5 were male (5/6). There were 4 patients with paroxysmal AF (4/6), and 2 patients with persistent AF (2/6). The mean CHA 2 DS 2 -VASc score was (4.8±1.5), and the HAS-BLED score was (3.5±1.4). The duration of hemodialysis was 2.6 (1.1, 8.3) years. Successfully Watchman implantation was achieved in all patients. There were no severe perioperative complications, and no device related thrombosis or leaks were observed by transesophageal echocardiography. During a mean of 22.0 (12.0, 32.0) months follow-up, there was no thromboembolism or major bleeding events. A total of 2 patients died, one from sudden cardiac death, and another one from heart failure. Conclusions: LAAO may be a safe and effective therapeutic option for prevention of thromboembolism in patients with atrial fibrillation and end-stage renal disease undergoing long-term hemodialysis, further studies with larger patient cohort are needed to confirm our results.

Although periprosthetic joint infection (PJI) has been hypothesized to increase the risk of complications following revision total knee arthroplasty (TKA), strong evidence linking the two is lacking. The aim of this study was to determine whether PJI is an independent risk factor for inpatient perioperative complications, and increased resource use in patients undergoing revision TKA. We relied on the US Nationwide Inpatient Sample (NIS) to identify patients with PJI or non-PJI treated with revision TKA between 2002 and 2014. Overall, 5,316 (16.4%) and 27,033 (83.6%) patients were categorized as PJI and non-PJI, respectively. To adjust for potential baseline differences between the two groups, propensity-score-based matching was performed. This resulted in 5,187 (50%) PJI patients matched to 5,187 (50%) non-PJI patients. The rates of postoperative complications, blood transfusions, prolonged length of stay (pLOS), in-hospital cost, and in-hospital mortality were assessed for both groups. Multivariable logistic regression analyses were performed within the cohort after propensity-score matching. For PJI versus non-PJI, respectively, the following rates were recorded: blood transfusions, 28.3 versus 18.4% ( p  < 0.0001); postoperative complications, 27.5 versus 19.8% ( p  < 0.0001); pLOS (>4 d), 61.9 versus 26.9% ( p  < 0.0001); in-hospital cost (>$39,929), 55.8 versus 44.2% ( p  < 0.0001); in-hospital mortality, 0.6 versus 0.3% ( p  = 0.016). In multivariable logistic regression analyses, PJI patients were more likely to receive a blood transfusion (odds ratio [OR]: 1.78; p  < 0.0001), to experience postoperative complications (OR: 1.56; p < 0.0001), to have a higher in-hospital cost (OR: 1.65; p < 0.0001), to have a pLOS following surgery following surgery (OR: 4.69; p  < 0.0001), and to have a higher in-hospital mortality (OR: 2.14; p  = 0.019). After adjustment for potential selection biases, PJI is associated with more adverse perioperative outcomes and resource use than non-PJI patients. This is a Level II (level of evidence), prognostic study., Competing Interests: None declared., (Thieme. All rights reserved.)

To evaluate the efficacy and safety of left atrial appendage occlusion (LAAO) in patients with atrial fibrillation (AF) over 75 years. A total of 82 patients with AF who underwent LAAO successfully in Beijing Anzhen Hospital from March 2014 to March 2019 were divided into two groups according to age: the elderly group (aged>75 years) and the young group (aged ≤75 years). Risk of perioperative complications and incidence of ischemic stroke and major bleeding during follow-up were retrospectively analyzed. The results showed that there were no significant differences in procedure-related ischemic stroke(0 vs.1.6%, P =0.768) and major bleeding (0 vs.1.6%, P =0.768) during perioperative period between the two groups. No complications as death or pericardial tamponade occurred in the two group. During a (25.9±15.9) months period of followed up, ischemic stroke event rate was 3.6/100 person-years in the elderly group and 4.9/100 person-years in the young group, respectively. Major bleeding event rate was 2.5/100 person-years in the elderly group and 0/100 person-years in the young group, respectively. Compared with the expected ones, the relative risk reduction (RRR) of stroke in the elderly group was more profound than that in the young group (32.0% vs. 25.0%), while the risk of major bleeding in the young group was significantly lower than that in the elderly group (RRR 100% vs. 56.9%). Therefore, LAAO might be suitable for stroke prevention in the elderly AF patients.

The directional synthesis of transition metal phosphides was considered to be an effective strategy to solve the overdependence of noble metals on photocatalytic hydrogen evolution (PHE) reactions. Inspiringly, this work reported a facile method for constructing hollow Co 2 P nanocages (Co 2 P NCGs) that derived from ZIF-67 by calcining and phosphiding procedure in nitrogen atmosphere to act as non-noble metal cocatalysts. Followed with further coating thin-layered ZnIn 2 S 4 (ZIS) on the surface of Co 2 P NCGs through a hydrothermal reaction, the hierarchical robust Co 2 P/ZnIn 2 S 4 nanocages (Co 2 P/ZIS NCGs) were then delicately fabricated as efficient photocatalysts for PHE reactions. The uniquely hollow structure of Co 2 P NCGs largely diffused the photogenerated chargers that induced from ZIS and the closely interfacial contact significantly promoted the separation and transfer of electrons from ZIS to Co 2 P according to density functional theory (DFT) calculation, synergistically resulting in an efficient hydrogen generation performance. PHE results showed that an efficient H 2 evolution rate of 7.93 mmol/g/h over 10% Co 2 P/ZIS NCGs was achieved, about 10 times higher than that of pristine ZnIn 2 S 4 . More importantly, the hierarchically hollow Co 2 P/ZIS NCGs exhibited ascendant PHE activity in comparison with that of 1% noble metal (Pt, Au, Ag) loaded ZnIn 2 S 4 with superior sustainability, all indicating the efficient and stable photocatalysts of Co 2 P/ZIS NCGs for PHE reactions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The photocatalytic evolution of hydrogen (H 2 ) from water splitting is considered a promising route to overcome the energy crisis, and the key lies in the preparation of efficient photocatalysts. Herein, superior ordered sponge-like carbon self-doped graphitic carbon nitride (g-C 3 N 4 ) nanosheets (SCCNS) were prepared via a combined strategy of melamine-cyanuric acid complex supramolecular pre-assembly and solvothermal pre-treatment using ethylene glycol (EG) aqueous solutions (EG:water = 50:50 vol.%) as a solvent and carbon doping source. The following pyrolysis converts the naturally arranged melamine-EG-cyanuric acid supramolecular intermediates to highly crystalline SCCNS with large specific surface areas. The optimal SCCNS-180 exhibits superior photocatalytic H 2 evolution activities (∼4393 and 11 320 μmol h -1 g -1 ) when irradiated with visible light and simulated sunlight; these values are up to ∼17- and ∼18-fold higher than that of bulk g-C 3 N 4 . The quantum efficiency of SCCNS-180 at λ = 420 nm can reach 6.0%. The excellent photocatalytic performance of SCCNS-180 derives from its distinct ordered sponge-like nanosheet structure with highly crystallinity and the carbon doping, leading to its improved optical absorption, accelerated photoinduced electron-hole pair transfer and separation rate and enlarged specific surface area (134.4 m 2 g -1 ).

Objective: To investigate the efficacy and safety of idarucizumab in the treatment of perioperative cardiac tamponade and thromboembolic events during catheter ablation in atrial fibrillation (AF) patients under dabigatran therapy. Methods: This study was a retrospective analysis enrolling patients under dabigatran therapy, who underwent catheter ablation for AF at Beijing Anzhen Hospital from January 2019 to December 2020 and developed perioperative cardiac tamponade or acute ischemic stroke (AIS) and received idarucizumab to reverse the anticoagulant effect of dabigatran. Patients' age, sex, renal function, coagulation test and safety events at 30 d after idarucizumab administration were collected and analyzed. The clinical presentation and prognosis were also analyzed. Results: A total of 7 patients were included, 2 (2/7) were male, mean age was (66.3±11.2) years, serum creatinine level was (66.3±13.6) μmol/L, estimated glomerular filtration rate was (89.4±11.2) ml·min -1 ·1.73 m -2 , CHA 2 DS 2 -VASc and HAS-BLED scores were (3.2±1.9) and (1.3±1.3), respectively. Five patients (5/7) developed cardiac tamponade during the perioperative period and the time interval to the last dose of dabigatran was (6.3±2.6) h. Idarucizumab was given at (36.4±16.7) min after the definitive diagnosis of cardiac tamponade. A significant decrease of activated partial thromboplastin time was achieved after idarucizumab administration in all five cases. Pericardial puncture and drainage were applied to all patients (5/5) with cardiac tamponade, the drainage volume was (1 037.0±846.9) ml, the retention time of pericardial drainage catheter was (27.9±13.9) h, and the recovery time of anticoagulation was (28.4±13.2) h. One patient (1/5) underwent thoracotomy for hemostasis due to excessive blood loss with the aim of ensuring complete hemostasis. Bleeding occurred in 1 patient (1/5) after the first restart of anticoagulation. AIS occurred in 2 patients (2/7) after operation. One case (1/2) received intravenous thrombolysis after receiving 5.0 g idarucizumab, no hemorrhagic transformation was observed, and the recovery process was satisfactory. Another patient in this group experienced significantly prolonged onset time and 5.0 g idarucizumab was applied before intravascular thrombectomy, there was no bleeding complication in this patient after thrombectomy. At the time of discharge, the consciousness was not significantly improved, and the muscle strength of the right lower limb was recovered somehow compared with that before operation. No hypersensitivity reactions or thrombotic events occurred in these patients within 30 days of the administration of idarucizumab. Conclusion: In AF catheter ablation-associated cardiac tamponade and AIS, idarucizumab is safe and effective in rapidly reversing the anticoagulant effect of dabigatran, use of thrombectomy saves valuable time for timely hemostasis and improvement of cerebral blood circulation.

The conventional preparation of SnNb 2 O 6 invariably involves complex and laborious steps, which unavoidably introduces defect into the host lattice and also increases the reaction period and costs, resulting in undesired recombination of photo-generated electron-hole pairs. For the first time in this work, we manage to synthesize single-crystalline two-dimensional (2D) SnNb 2 O 6 nanosheets with ultrathin structure through a facile one-step hydrothermal method. Comparative studies were explored to analyze the structure and phase evolution during the preparation course. The synthesized 2D structure demonstrated a narrower band gap of 2.09 eV and specific surface area of 76.1 m 2 g -1 , which exhibited significantly extended visible-light-responsive range and larger surface area by contrast with the state-of-the-art reports, resulting in excellent visible-light-driven photoactivity towards H 2 production and water purification as well. Additionally, further enhanced photocatalytic performance was achieved by the incorporation of Pt as co-catalyst to indirectly indicate the advantage of the SnNb 2 O 6 nanosheets in this method over other reported counterparts. It was found that, a very small amount of Pt loaded on the surface of SnNb 2 O 6 nanosheets would contribute to remarkably higher activity than pure SnNb 2 O 6 nanosheets and exhibit superior stability as well. Moreover, a deep insight into the underlying photocatalytic mechanism was proposed. This work sheds light on a new facile way to fabricate high-performance photocatalytic materials and provided new opportunities for solar-energy conversion.

Dopamine D1 receptor (D1DR) and D2 receptor (D2DR) are closely associated with pain modulation, but their exact effects on neuropathic pain and the underlying mechanisms remain to be identified. Our research revealed that intrathecal administration of D1DR and D2DR antagonists inhibited D1-D2DR complex formation and ameliorated mechanical and thermal hypersensitivity in chronic constriction injury (CCI) rats. The D1-D2DR complex was formed in the rat spinal cord, and the antinociceptive effects of D1DR and D2DR antagonists could be reversed by D1DR, D2DR, and D1-D2DR agonists. Gαq, PLC, and IP3 inhibitors also alleviated CCI-induced neuropathic pain. D1DR, D2DR, and D1-D2DR complex agonists all increased the intracellular calcium concentration in primary cultured spinal neurons, and this increase could be reversed by D1DR, D2DR antagonists and Gαq, IP3, PLC inhibitors. D1DR and D2DR antagonists significantly reduced the expression of p-PKC γ, p-CaMKII, p-CREB, and p-MAPKs. Levo-corydalmine (l-CDL), a monomeric compound in Corydalis yanhusuo W.T. Wang, was found to obviously suppress the formation of the spinal D1-D2DR complex to alleviate neuropathic pain in CCI rats and to decrease the intracellular calcium concentration in spinal neurons. l-CDL-induced inhibition of p-PKC γ, p-MAPKs, p-CREB, and p-CaMKII was also reversed by D1DR, D2DR, and D1-D2DR complex agonists. In conclusion, these results indicate that D1DR and D2DR form a complex and in turn couple with the Gαq protein to increase neuronal excitability via PKC γ, CaMKII, MAPK, and CREB signaling in the spinal cords of CCI rats; thus, they may serve as potential drug targets for neuropathic pain therapy.

Purpose: This systematic review aimed to examine the evidence on adventure therapy (AT) intervention for child, adolescent, and young adult (AYA) cancer patients in order to inform the design of future research and clinical practice., Methods: This review included studies that tested the AT intervention among child and AYA cancer patients. Nine electronic databases (CINAHL, Cochrane Central Register of Controlled Trials, EMBase, Medline via EbscoHost, OpenGrey, PsycInfo, Web of Science, Scopus, and PubMed) were searched for English-language published studies using a quasi-experimental design, one-group pre-test-post-test experimental study design, or randomized controlled trial (RCT) from 1981 to May 2020. The methodological quality of the included studies was evaluated using JBI Critical Appraisal Checklists for RCTs and for Quasi-Experimental Studies by two researchers independently. A narrative synthesis of intervention characteristics and related health-related outcomes was performed., Results: Eight papers from seven studies were included in the review, namely four RCTs, two quasi-experimental study papers, and two one-group pre-test-post-test experimental study papers. Studies varied in the components and duration of AT. Medium to high methodological quality of included studies was noted in all study designs. Results showed the positive effects of AT on the physical activity, fatigue, psychological distress, and quality of life of child and AYA cancer patients., Conclusion: AT is a promising intervention that may improve a number of health-related outcomes in child and AYA cancer patients. Evidence-based AT interventions should be developed and incorporated as part of supportive care for the target population.

Recent studies showed that the deubiquitinase ubiquitin-specific protease 34 (USP34) was involved in the tumorigenesis of several tumors, but its function and mechanism are still unclear in laryngeal squamous cell carcinoma (LSCC). In this study, we found that USP34 and SOX2 were elevated in LSCC tumor tissues, and we also found that USP34 expression was positively correlated with SOX2 expression. Our further studies showed that USP34 regulated the protein level of SOX2 in LSCC cells, but not the mRNA level, which suggested that USP34 stabilized SOX2. Moreover, USP34, as a deubiquitinase, could interact with SOX2, and reduce the polyubiquitination of SOX2. In addition, knockdown of USP34 could significantly inhibit LSCC cell growth, but overexpression of SOX2 could reverse this effect. Finally, we also found that USP34 and SOX2 were upregulated in cisplatin-resistant LSCC cells, but knockdown of USP34 could enhance the drug sensitivity of cisplatin in the resistant cells. Collectively, targeting USP34/SOX2 axis may be a promising strategy for the treatment of LSCC., (© 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Background and Objectives: Gap junctions play a pivotal role in contributing to the formation of astroglial networks and in chronic pain. However, the mechanisms underlying the dysfunction of astroglial gap junctions in chronic pain have not been fully elucidated., Methods: Chronic constriction injury (CCI) of the sciatic nerve was used to establish rat neuropathic pain model. C6 cells were used to perform experiments in vitro. Von Frey hairs and Hargreave's method were used to determine the withdrawal threshold of rats. Protein expression was detected by immunofluorescence and western blotting., Results: Astragaloside IV (AST IV) significantly attenuated neuropathic pain and suppressed the excitation of spinal astrocytes in rats with CCI. The antinociceptive effect of AST IV was reversed by the gap junction decoupler carbenoxolone (CBX). AST IV inhibited the high expression of phosphorylated connexin 43 (p-Cx43) and p-c-Jun N-terminal kinase (p-JNK) in spinal cord of rats with CCI. JNK inhibitor alleviated neuropathic pain, which was reversed by CBX. JNK inhibitor decreased the high expression of p-Cx43 in both rats with CCI and tumor necrosis factor-alpha (TNF-α)-treated C6 cells. Additionally, the analgesic effect of AST IV was reversed by the adenosine triphosphate-sensitive potassium (K ATP ) channel blocker, glibenclamide (Glib). Glib abolished the inhibitory effects of AST IV on p-JNK and p-Cx43 both in vivo and in vitro. K ATP channel opener (KCO) mimicked the inhibitory effects of AST IV on p-JNK and p-Cx43 in TNF-α-treated C6 cells., Conclusion: Our results indicate that the sciatic nerve CCI induces the dysfunction of gap junctions in the spinal cord by activating K ATP /JNK signaling to contribute to neuropathic pain. AST IV attenuates neuropathic pain via regulating the K ATP -JNK gap junction axis., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Accessory pathways (APs) successfully ablated at the aortomitral continuity (AMC) were sporadically reported but relevant data are very limited. We aimed to describe the electrophysiological characteristics of AMC-AP and the related anatomy., Methods and Results: This study involved eight (male/female = 3/5, mean age 42.6 ± 10.5 years) patients with left-sided AP successfully ablated in the AMC region. The retrograde atrial activation sequence was analysed and compared via recordings at the His-bundle (HB), coronary sinus (CS), and roving catheter during tachycardia, and the peak of QRS from the same cardiac circle used as time reference. Of the eight patients, two received prior ablations. During tachycardia, the activation time at the proximal CS (CSp), lateral CS (CSl), and HB region averaged 120 ± 26 ms, 124 ± 29 ms, and 117 ± 21 ms following the reference, respectively (P = 0.86). The latest atrial activation was recorded in the posterior CS which averaged 135 ± 25 ms following the reference. Placing the ablation catheter to AMC via retrograde approach was attempted in all cases but stable positioning achieved in none. Via transseptal approach, the ablation catheter could be easily placed at the AMC and recorded the earliest retrograde atrial activations with 60 ± 27 ms earlier than the relatively 'earliest' CS/HB recordings, and ablation at this site successfully eliminated AP conduction. No patients had recovered AP conduction after at least 12-month follow-up., Conclusion: AMC-AP is featured by recording comparable retrograde atrial activation times at CSp, CSl, and HB with the latest recordings at the posterior CS. Stable placement and successful ablation in the AMC via retrograde aortic approach was difficult but can be achieved via transseptal approach., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Venous thromboembolism (VTE; deep venous thrombosis and pulmonary embolism) is a known complication following primary total knee arthroplasty (TKA). The aim of this study was to investigate the trends of the incidence of VTE after primary TKA and identify associated risk factors for the occurrence of VTEs in a large cohort of TKA patients. We performed a retrospective study in which the Nationwide Inpatient Sample (NIS) database was used to identify all patients who underwent primary TKA over a period of 13 consecutive years (between 2002 and 2014) in the United States. The occurrence of a symptomatic VTE was identified with the use of ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) diagnosis codes. A total of 1,460,901 primary TKA procedures were identified in the NIS from 2002 to 2014, and 12,944 of these patients were recorded as having 13,855 VTEs, consisting of 7,609 deep venous thromboses (0.52%) and 6,246 pulmonary emboli (0.43%). The overall VTE incidence in patients undergoing TKA in the United States from 2002 to 2014 was 0.89%. Patient-related risk factors for VTEs include an older age (odds ratio [OR]: 1.44; 95% confidence interval [CI]: 1.31-1.59), black race (OR: 1.34; 95% CI: 1.25-1.44), and Medicare insurance (OR: 1.18; 95% CI: 1.13-1.22). Most of the comorbidities were associated with an increased risk of VTE following TKA. Particularly, cardiac arrhythmias, coagulopathy, fluid and electrolyte disorders, pulmonary circulation disorders, and weight loss increased the risk of VTE by more than twofold. After adjusting for confounders, VTE was associated with a longer hospital stay (2.81 ± 0.02 day), increased costs (US$14,212.16 ± US$255.64), and higher mortality rate (OR: 13.04; 95% CI: 11.08-15.35). This nationally representative study of inpatients in the United States identified several independent risk factors for VTE perioperatively in TKA patients and provided evidence that VTE patients after TKA are likely to have worse results than non-VTE patients with regard to the length of hospital stay, hospital costs, and inhospital mortality. This is a level III, prognostic study., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Revision total hip arthroplasty (THA) remains a significant challenge when there is severe femoral bone loss. The purpose of this study was to evaluate the clinical and radiographic outcomes of revision THA in patients with femoral bone loss treated with Zweymüller SLR-Plus stem., Methods: A retrospective review of 82 patients who underwent revision THA using tapered rectangular femoral stem between 1997 and 2007 was undertaken. Of the 82 patients, 9 patients were lost to follow-up and were excluded from the study. The most common reason for revision was aseptic loosening (92%), periprosthetic femur fracture (5%), and infection (3%). Bone loss was categorised preoperatively according to the Paprosky classification. The mean clinical follow-up was 14 years (range 10-19 years). Their mean age at the time of index surgery was 54.7 ± 15.3 (range 30-82) years., Results: The mean Harris Hip Score was significantly improved at final follow-up (68.1 ±10.3) compared with that before the revision surgery (30.4 ± 7.7) ( p < 0.0001). Of the 75 stems, 69 (92%) stems were radiographically stable at the last evaluation. Among the 69 stems, 64 hips (85%) had radiographic evidence of bone ingrowth and 5 (5%) had stable fibrous fixation of the stem. Among the 7 hips that were re-revised, 5 hips were re-revised for aseptic loosening, whereas 2 were re-revised for an infection. Kaplan-Meier survivorship analysis, with removal of the stem for any cause as the endpoint, revealed that the 15-year rate of survival of the components was 90% (95% CI, 0.83-0.97)., Conclusion: Revision THA in patients with proximal femoral bone loss using Zweymüller SLR-Plus stem led to a high rate of osseointegration of the stem and good clinical results at long-term follow-up.

Introduction: Spinal N-methyl-D-aspartate receptor (NMDAR) is vital in chronic pain, while NMDAR antagonists have severe side effects. NMDAR has been reported to be controlled by G protein coupled receptors (GPCRs), which might present new therapeutic targets to attenuate chronic pain. Dopamine receptors which belong to GPCRs have been reported could modulate the NMDA-mediated currents, while their exact effects on NMDAR in chronic bone cancer pain have not been elucidated., Objectives: This study was aim to explore the effects and mechanisms of dopamine D1 receptor (D1DR) and D2 receptor (D2DR) on NMDAR in chronic bone cancer pain., Methods: A model for bone cancer pain was established using intra-tibia bone cavity tumor cell implantation (TCI) of Walker 256 in rats. The nociception was assessed by Von Frey assay. A range of techniques including the fluorescent imaging plate reader, western blotting, and immunofluorescence were used to detect cell signaling pathways. Primary cultures of spinal neurons were used for in vitro evaluation., Results: Both D1DR and D2DR antagonists decreased NMDA-induced upregulation of Ca 2+ oscillations in primary culture spinal neurons. Additionally, D1DR/D2DR antagonists inhibited spinal Calcitonin Gene-Related Peptide (CGRP) and c-Fos expression and alleviated bone cancer pain induced by TCI which could both be reversed by NMDA. And D1DR/D2DR antagonists decreased p-NR1, p-NR2B, and Gαq protein, p-Src expression. Both Gαq protein and Src inhibitors attenuated TCI-induced bone cancer pain, which also be reversed by NMDA. The Gαq protein inhibitor decreased p-Src expression. In addition, D1DR/D2DR antagonists, Src, and Gαq inhibitors inhibited spinal mitogen-activated protein kinase (MAPK) expression in TCI rats, which could be reversed by NMDA., Conclusions: Spinal D1DR/D2DR inhibition eliminated NMDAR-mediated spinal neuron activation through Src kinase in a Gαq-protein-dependent manner to attenuate TCI-induced bone cancer pain, which might present a new therapeutic strategy for bone cancer pain., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors. Published by Elsevier B.V. on behalf of Cairo University.)

Background: Anti-nerve growth factor (NGF) monoclonal antibodies (anti-NGF mAbs) have been reported to significantly attenuate pain, but the mechanism involved has not been fully elucidated, and the serious adverse events associated with mAbs seriously limit their clinical use. This study further investigated the mechanism by which peripheral NGF is involved in neuropathic pain and found safe, natural compounds that target NGF to attenuate neuropathic pain., Methods: Nociception was assessed by the Von Frey hair and Hargreaves' methods. Western-blotting, qPCR and immunofluorescence were used to detect the cell signaling pathway. RAW264.7 macrophages and RSC96 Schwann cells were cultured for in vitro evaluation., Results: Intraplantar administration of anti-NGF mAbs suppressed the expression of phosphorylated transforming growth factor-β-activated kinase 1 (TAK1) in the dorsal root ganglion (DRG) and sciatic nerve. Intraplantar administration of a TAK1 inhibitor attenuated CCI-induced neuropathic pain and suppressed the expression of phosphorylated mitogen-activated protein kinases (MAPKs) in the DRG and sciatic nerve. Perisciatic nerve administration of levo-corydalmine (l-CDL) on the operated side obviously attenuated CCI-induced neuropathic pain and suppressed the expression of mNGF and proNGF. In addition, l-CDL-induced antinociception was reversed by intraplantar administration of NGF. Further results indicated that l-CDL-induced suppression of phosphorylated TAK1, MAPKs, and p65 and expression of the proinflammatory cytokines TNF-α and IL-1β in the DRG and sciatic nerve were all abolished by NGF. In addition, in vitro experiments indicated that l-CDL suppressed the secretion of NGF and proNGF in RAW264.7 macrophages and RSC96 Schwann cells, which was abolished by AP-1 and CREB agonists, respectively., Conclusions: This study showed NGF inhibition suppressed TAK1 in the periphery to attenuate CCI-induced neuropathic pain through inhibition of downstream MAPK and p65 signaling. The natural compound l-CDL inhibited NGF secretion by macrophages and Schwann cells and downstream TAK1-MAPK/NF-κB signaling in the periphery to attenuate CCI-induced neuropathic pain. Video abstract Proposed mechanisms underlying the effect of l-CDL in periphery of CCI rats. In CCI rats, macropahages and Schwann cells could secret NGF to act on the receptors in the periphery to activate TAK1-MAPK/NF-κB axis and promote the release of proinflammatory cytokines, including TNF-α and IL-1β to promote neuropathic pain. l-CDL decreased the secretion of NGF through inhibiting AP-1 and CREB respectively in RAW264.7 and RSC96 Schwann cells to attenuate CCI-induced neuropathic pain by inhibiting the TAK1-p38 MAPK/NF-κB signaling pathway.

Background and Objectives: Neuropathic pain is partially refractory to currently available treatments. Although some studies have reported that apoptosis signal-regulating kinase 1 (ASK1) may inhibit chronic pain, the mechanisms underlying this process have not been fully elucidated., Methods: Chronic constriction injury (CCI) of the rat sciatic nerve was used to establish a neuropathic pain model. Nociception was assessed using von Frey hair and Hargreaves' methods. Western blot and immunofluorescence were used to detect the cell signaling pathway. BV2 cell line was cultured for in vitro evaluation., Results: Our results indicated that spinal ASK1 was co-expressed with the microglia marker ionized calcium binding adaptor 1. Additionally, intrathecal administration of ASK1 inhibitor suppressed the activation of spinal microglia and attenuated CCI-induced neuropathic pain. The ASK1 inhibitor also decreased the levels of phosphorylated ASK1 (p-ASK1), p65, p38 mitogen-activated protein kinase (MAPK) and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) messenger RNA in lipopolysaccharide-stimulated BV2 microglia cells. Intragastric administration of levo -corydalmine ( l -CDL) significantly attenuated CCI-induced neuropathic pain and inhibited the expression of p-ASK1 in the spinal cord. l -CDL conspicuously suppressed the activation of spinal microglia in vitro and in vivo. Translocation of nuclearfactor-kappa B (NF-κB) and upregulation of p-p65, TNF-α, IL-1β were inhibited by l- CDL. Further, the analgesic effects of l -CDL were associated with reduced levels of phosphorylated protein kinase C (PKC γ), c-JunNH2-terminal kinase, and extracellular signal-regulated kinase., Conclusions: This study showed that the expression of ASK1 in spinal microglia and ASK1 inhibitor suppressed microglia activation via suppression of p38 MAPK/NF-κB, which ultimately attenuated CCI-induced neuropathic pain. l- CDL also inhibited the ASK1-P38 MAPK/NF-κB axis to attenuate CCI-induced neuropathic pain., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore the safety and effectiveness of left bundle branch area pacing (LBBAP) in children. Methods: Clinical data, pacing electrocardiogram and parameters of 6 patients (5 females and 1 male) who underwent permanent pacemaker implantation and LBBAP from January to June 2019 in the Department of Pediatric Cardiology of Anzhen Hospital were retrospectively analyzed. Results: The weight of the 6 patients aged between 9 and 14 years ranged from 26 to 48 kg. Five patients were diagnosed with third degree atrioventricular block, and 1 patient was diagnosed with cardiac dysfunction after right ventricular apical pacing. Cardiac function decreased in one patient and remained normal in the other five patients. Left ventricular end diastolic diameter (LVEDD) Z score was 1.85±0.65. V(1) lead showed changes like right bundle branch block in pacing electrocardiogram. No significant difference was found regarding QRS wave duration ((95±13) ms vs. (111±20) ms, t= -1.610, P> 0.05) between preoperation and postoperation. Pacing threshold was (0.85±0.26) V. The sensing threshold was (15.0±4.3) mV and the impedance was (717±72) Ω. P potential was recorded in 3 cases. The earliest left ventricular local activation time was (56±5) ms and remained stable at different output voltages. Postoperative echocardiography revealed that the electrodes were located near the endocardium of the left ventricular septum. No complications such as myocardial perforation and electrode dislocation occurred during follow-up. The pacing threshold, sensing threshold and impedance were (0.60±0.09)V, (16.1±3.9)mV, (662±78)Ω respectively at 3 months after operation. The patient with low left ventricular ejection fraction (LVEF) recovered to normal on the 3 rd day after LBBAP (45% vs. 57%). The LVEDD Z score decreased to (1.1±0.3) at 3 months after operation and was significantly lower than that before operation ( t= 2.38, P< 0.05). Conclusions: LBBAP in children can achieve narrow QRS pacing andphysiological pacing with stablepacing parameters. It can improve left ventricular enlargement caused by long-term bradycardia, and cardiac dysfunction and cardiac enlargement caused by long-term right ventricular apical pacing quickly and effectively.LBBAP is safe and feasible for older children in the near future. However, the long term potential risks of LBBAP need further observation and study.

Synovitis is an aseptic inflammation that leads to joint effusion, pain and swelling. As one of the main drivers of pathogenesis in osteoarthritis (OA), the presence of synovitis contributes to pain, incidence and progression of OA. In our previous study, DC32 [(9α,12α-dihydroartemisinyl) bis(2'-chlorocinnmate)], a dihydroartemisinin derivative, was found to have an antirheumatic ability via immunosuppression, but the effect of DC32 on synovitis has not been fully illuminated. In this study, we chose to evaluate the effect and mechanism of DC32 on attenuating synovial inflammation. Fibroblast-like synoviocytes (FLSs) of papain-induced OA rats were isolated and cultured. And DC32 significantly inhibited the invasion and migration of cultured OA-FLSs, as well as the transcription of IL-6, IL-1β, CXCL12 and CX3CL1 in cultured OA-FLSs measured by qPCR. DC32 remarkably inhibited the activation of ERK and NF-κB pathway, increased the expression of Nrf2 and HO-1 in cultured OA-FLSs detected by western blot. DC32 inhibited the degradation and phosphorylation of IκBα which further prevented the phosphorylation of NF-κB p65 and the effect of DC32 could be relieved by siRNA for Nrf2. In papain-induced OA mice, DC32 significantly alleviated papain-induced mechanical allodynia, knee joint swelling and infiltration of inflammatory cell in synovium. DC32 upregulated the mRNA expression of Type II collagen and aggrecan, and downregulated the mRNA expression of MMP2, MMP3, MMP13 and ADAMTS-5 in the knee joints of papain-induced OA mice measured by qPCR. The level of TNF-α in the serum and secretion of TNF-α in the knee joints were also reduced by DC32 in papain-induced OA mice. In conclusion, DC32 inhibited the inflammatory response in osteoarthritic synovium through regulating Nrf2/NF-κB pathway and attenuated OA. In this way, DC32 may be a potential agent in the treatment of OA., (Copyright © 2019. Published by Elsevier B.V.)

Blood glucose variability is considered to be one of the risk factors for coronary heart disease, and there is growing evidence that blood glucose fluctuation is closely related to the characteristics of plaques. The aim of the study was to investigate the influence of blood glucose variability on the vulnerability of culprit plaques in elderly non-ST segment elevation acute coronary syndrome (NSTE-ACS) patients.Coronary angiography and VH-IVUS were applied to evaluate the components of culprit plaque in NSTE-ACS patients. CGMS monitoring was performed for 72 hours and blood glucose variability was assessed by glycemic excursions (MAGE), absolute means of daily differences (MODD), postprandial glycemic excursions (PPGE), and the largest amplitude of glycemic excursions (LAGE). An oxidative stress indicator (urinary 8-iso-PGF 2α ) was also tested.Eighty two elderly NSTE-ACS patients were enrolled in this study. Higher glucose variability was associated with the increased culprit plaque instability. MODD was positively correlated with urinary 8-iso-PGF 2α . PPGE and urinary 8-iso-PGF 2α were independent risk factors for percent fibrous and necrotic volume in culprit plaques (PPGE: β = -0.340, P = 0.024; urinary 8-iso-PGF 2α : β = -0.294, P = 0.013).Blood glucose variability is positively related to oxidative stress. With an increase in blood glucose variability, the instability of criminal plaques in elderly NSTE-ACS patients increased.

Urinary excretion of 8-iso-prostaglandin F 2α (8-iso-PGF 2α ), a reliable biomarker for enhanced oxidant stress in vivo, has been described in association with diabetes and coronary heart disease. The aim of this study was to evaluate the relationship between urinary 8-iso-PGF 2α levels and the characteristics of coronary culprit lesion in diabetic patients with acute coronary syndrome (ACS). A total of 79 diabetic patients with ACS were included. iMAP intravascular ultrasound (iMAP-IVUS) was performed to evaluate the characteristics of culprit plaques. Fasting urinary 8-iso-PGF 2α level was measured and corrected by creatinine clearance. iMAP-IVUS data showed culprit plaques in high urinary 8-iso-PGF 2α level patients had a greater percentage of necrotic core and less fibrous components. High urinary 8-iso-PGF 2α levels were correlated with increased necrotic plaque components (r = 0.325, P = 0.003). Meanwhile, the presence of thin-capped fibroatheroma (50.0% versus 11.5%, P = 0.003), ruptured plaques (30.8% versus 7.7%, P = 0.035), and thrombus (38.5% versus 7.7%, P = 0.008) were significantly more frequent in the upper tertile of urinary 8-iso-PGF 2α levels than in the low tertile. Multivariate analysis showed high levels of urinary 8-iso-PGF 2α (OR 4.240, P = 0.007) was independently associated with the presence of vulnerable culprit plaque in diabetic ACS patients. Urinary 8-iso-PGF 2α also displayed a significant value in predicting vulnerable plaques in diabetic patients with ACS by constructing the receiver-operating characteristic (ROC) curve (Area under the ROC curve: 0.713, P = 0.001). Urinary 8-iso-PGF 2α levels are associated with the vulnerability of the coronary culprit lesion in diabetic patients with ACS and may provide additional information for risk assessment in suspected vulnerable patients.

Background: To evaluate the clinical results of arthroscopic repair with or without platelet-rich plasma (PRP) for tears of the discoid lateral meniscus (DLM)., Methods: Twenty-nine patients with DLM tears within a stable knee were arthroscopically treated with meniscal suture repair. Of those, 14 were augmented with platelet-rich plasma (PRP), and 15 were performed without PRP augmentation. Patients were evaluated at baseline (the day before surgery) and then 12 and 24 months after the last injection. Evaluation included the Lysholm score, and Ikeuchi grade, Visual analogue score (VAS) for pain and failure rate. Failure was defined by patients developing symptoms of joint line pain, locking, swelling or requiring repeat arthroscopy., Results: There was no difference in the failure rate in the PRP group (1 of 14) compared with the non-PRP group (2 of 15) (P = 0.58). Statistically significant improvement in Lysholm score, Ikeuchi grade and VAS for pain was documented at the last follow-up compared with baseline in both PRP and non-PRP group. No significantly difference was found between the PRP group and non-PRP group on Lysholm score, Ikeuchi grade and VAS for pain at the last follow-up. In the univariate analysis of each variable, younger age (P = 0.036) and longer follow-up duration (P = 0.043) were statistically associated with a better function improvement. Whereas in multivariate analysis, only younger age (P = 0.004) was significantly associated with a better function improvement., Conclusion: With regard to clinical evaluations in arthroscopic repair for DLM tears, PRP group had similar effect in pain relief and functional improvement to non-PRP group at mid-term follow-up. Future larger prospective studies with a longer follow-up are needed to determine whether PRP should be used with DLM repair.

A novel electrocatalytic system was developed to realize one-pot conversion of organic pollutants into liquid fuels such as methanol (CH 3 OH) and ethanol (C 2 H 5 OH). The process combines the catalytic oxidation of organic pollutants with electrocatalytic reduction of CO 2 . We first coupled the electrocatalytic process with SO 4 •- -based advanced oxidation processes (AOPs) for the degradation of 4-nitrophenol (4-NP) using a 3D-hexagonal Co 3 O 4 anode. In this step, 4-NP was mineralized to CO 2 , and then the CO 2 was converted to CH 3 OH and C 2 H 5 OH by electrocatalytic reduction using a flower-like CuO cathode. The experimental results show the destruction of 4-NP (60 mL, 10 mg/L) can be as high as 99%. In addition, the yields of CH 3 OH and C 2 H 5 OH were 98.29 μmol/L and 40.95 μmol/L, respectively, which represents a conversion of 41.8% of 4-NP into liquid fuels; the electron efficiency was 73.1%. In addition, we found that 3D-hexagonal arrays of Co 3 O 4 with different morphologies can be obtained by adding different amounts of urea. We also investigated the formation mechanism of novel 3D-hexagonal Co 3 O 4 arrays for the first time. A mechanism was proposed to explain the electrocatalytic steps involved in the conversion of 4-NP to CH 3 OH and C 2 H 5 OH and the synergetic effects between AOPs and electrocatalysis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The purpose of this study was to use meta-analytic approach to compare the efficacy and safety of intraarticular hylan and hyaluronic acid (HA) for knee osteoarthritis (OA) treatment. We searched PubMed, Embase, and the Cochrane databases through July 2017 to identify Level I randomized controlled trials (RCTs) that evaluated clinical efficacy and safety of hylan compared with HA for knee OA. The primary outcomes were Visual Analogue Scale (VAS) for pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, and WOMAC function scores. In each study and for the outcome measures (VAS for pain, WOMAC pain, function and stiffness scores, and Lequesne score), we calculated the treatment effect from the difference between the preintervention and postintervention changes in the hylan and HA groups. Twenty-one RCTs involving 3,058 patients were included. Pooled analysis suggested that compared with HA, hylan was associated with similar pain relief and function improvement in patients with knee OA (VAS for pain: mean difference [MD], -3.04; 95% confidence interval [CI], -9.13 to 3.04; p  = 0.33; I 2  = 76%. WOMAC pain score: MD, 0.23; 95% CI, -0.25 to 0.70; p  = 0.35; I 2  = 0%. WOMAC function score: MD, -0.47; 95% CI, -6.81 to 5.88; p  = 0.88; I 2  = 84%). No significant difference was found comparing the patients with treatment-related adverse events. The relationship was robust in sensitivity analysis and consistent in most of the subgroup analyses. As to the primary outcomes (WOMAC pain, function scores, VAS for pain), the difference between hylan and HA did not reach the previously reported minimum clinically important difference (MCID) values (-13.4 for VAS for pain, -2.0 for WOMAC pain score, -7.7 for WOMAC function score). Our meta-analysis showed that there were no statistically and clinically significant differences in pain relief and function improvement between hylan and HA injections for knee OA treatment. In view of its higher costs, we discourage the use of hylan in patients with knee OA in clinical practice. The level of evidence is I, meta-analysis of Level I studies., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

We evaluated the association of urinary excretion of 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) with the vulnerability of culprit lesions in 156 age- and sex-matched diabetic stable coronary artery disease (CAD) patients with or without thin-capped fibroatheroma (TCFA) identified by iMAP intravascular ultrasound. Fasting urinary 8-iso-PGF 2α level was measured and corrected by creatinine clearance. Compared to non-TCFA group, patients with TCFA had higher urinary 8-iso-PGF 2α levels [114.6 (71.1, 181.5) vs. 83.0 (63.2, 138.2) pmol/mmolCr, P = 0.012]. Urinary 8-iso-PGF 2α level was positively correlated with percent necrotic volume of culprit lesion (r = 0.218, P = 0.006). High urinary 8-iso-PGF 2α level (OR 2.941, P = 0.009) was independently associated with the presence of TCFA and displayed a significant value in predicting TCFA plaques in study patients. The current study indicated that urinary 8-iso-PGF 2α may be an important surrogate marker for the vulnerability of culprit lesion in diabetic patients with CAD., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Morphine tolerance remains a challenge in the management of chronic pain in the clinic. As shown in our previous study, the dopamine D2 receptor (D2DR) expressed in spinal cord neurons might be involved in morphine tolerance, but the underlying mechanisms remain to be elucidated. In the present study, selective spinal D2DR blockade attenuated morphine tolerance in mice by inhibiting phosphatidylinositol 3 kinase (PI3K)/serine-threonine kinase (Akt)-mitogen activated protein kinase (MAPK) signaling in a μ opioid receptor (MOR)-dependent manner. Levo-corydalmine (l-CDL), which exhibited micromolar affinity for D2DR in D2/CHO-K1 cell lines in this report and effectively alleviated bone cancer pain in our previous study, attenuated morphine tolerance in rats with chronic bone cancer pain at nonanalgesic doses. Furthermore, the intrathecal administration of l-CDL obviously attenuated morphine tolerance, and the effect was reversed by a D2DR agonist in mice. Spinal D2DR inhibition and l-CDL also inhibited tolerance induced by the MOR agonist DAMGO. l-CDL and a D2DR small interfering RNA (siRNA) decreased the increase in levels of phosphorylated Akt and MAPK in the spinal cord; these changes were abolished by a PI3K inhibitor. In addition, the activated Akt and MAPK proteins in mice exhibiting morphine tolerance were inhibited by a MOR antagonist. Intrathecal administration of a PI3K inhibitor also attenuated DAMGO-induced tolerance. Based on these results, l-CDL antagonized spinal D2DR to attenuate morphine tolerance by inhibiting PI3K/Akt-dependent MAPK phosphorylation through MOR. These findings provide insights into a more versatile treatment for morphine tolerance.

We report a feasible strategy via hydrothermal crystallization to activate Kagome lattice-structured Cu3V2O7(OH)2·2H2O volborthite mineral as a stable visible-light-driven photocatalyst. It was demonstrated to play a crucial role in stimulating absorption ability and photodegradation performance for the removal of methylene blue present in high concentration. In contrast, direct calcination was almost ineffective, whereas post-calcination was significantly detrimental. Moreover, the photocatalytic water oxidation activity of hydrothermally crystallizated volborthite was comparable to that of BiVO4, and it was clearly higher than those of WO3 and g-C3N4 from aqueous NaIO3 solution. By further in situ decoration with an optimum amount of CoOx cocatalysts (i.e., 2 wt%), the oxygen evolution rate of volborthite was greatly enhanced, and it was 1.6-fold, 1.8-fold and 2.9-fold higher than those of BiVO4, WO3 and g-C3N4, respectively. The importance of hydrothermal crystallization can be elucidated in terms of water-Kagome lattice structure interactions involving built-in intrinsic electric field and formation of single hydrogen bonds.

The use of tranexamic acid (TXA) during primary total knee arthroplasty (TKA) is well documented. However, considering the potential side effects, including deep vein thrombosis (DVT) and pulmonary embolism (PE), the ideal route of administration remains controversial. Therefore, we performed a meta-analysis to compare the efficacy of topical versus intravenous TXA and explore the most effective regimen in patients undergoing primary TKA. We conducted a systematic literature search in PubMed, Embase, and the Cochrane database through July 2016 to identify randomized controlled trials (RCTs) evaluating the efficacy and safety of topical and intravenous TXA in primary TKA. We assessed the risk of bias using the Cochrane Collaboration's tool. We assessed the quality of evidence using the GRADE profiler software. A total of 15 RCTs including 1,240 participants met the inclusion criteria. We found no statistically significant difference between topical and intravenous TXA in terms of transfusion rate ( p  = 0.75), total blood loss ( p  = 0.51), total drain output ( p  = 0.60), maximum hemoglobin drop ( p  = 0.24), length of stay ( p  = 0.08), and thromboembolic complications ( p  = 0.73). Subgroup analyses showed that compared with 1 g topical TXA, 2 g topical TXA was more effective to reduce blood transfusion rate and total blood loss, and did not increase thromboembolic complications. We also found three times intravenous TXA was more effective than one time of intravenous TXA to reduce blood transfusion rate and total blood loss without increasing of thromboembolic complications. Topical TXA had a similar efficacy to intravenous TXA in reducing blood transfusion and blood loss, and did not increase the risk of thromboembolic complications in primary TKA. Besides, the current meta-analysis suggested that three times of intravenous TXA is efficient and safe. We also recommended 2 g topical TXA instead of 1 g topical TXA because it was more efficient to reduce blood transfusion rate and total blood loss and did not increase thromboembolic complications., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Partial and total meniscectomies are the most common treatments for patients with discoid lateral meniscus (DLM). We conducted this study to quantitatively assess and compare the outcomes of partial and total meniscectomies for DLM. We also assessed whether the outcomes differed by the type of DLM, duration of follow-up, and age of patients. We searched PubMed, Embase, and the Cochrane database to identify relevant studies that reported outcomes, including Ikeuchi grade, the International Knee Documentation Committee (IKDC) Subjective Knee score, Lysholm score, or failure rate, in patients who underwent partial and total meniscectomies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes, whereas mean difference and 95% CIs were calculated for continuous outcomes. Fifteen studies met the inclusion criteria. The overall rate of excellent (E) or good (G) postoperatively was 85.5% (95% CI: 79.5-91.5%). The E or G rate of partial meniscectomy was significantly higher than that of total meniscectomy (OR= 1.97, 95% CI: 1.03-3.75, p  = 0.038). Besides, patients younger than 20 years had a significantly higher E or G rate than those older than 20 years. (OR = 3.12, 95% CI: 1.18-8.23, p  = 0.022). We also found the E or G rate tended to decrease from short- to long-term follow-up. Our systematic review and meta-analysis showed that that partial meniscectomy could achieve better outcomes compared with total meniscectomy for DLM patients., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Bone cancer pain is a challenge for its not completely clarified mechanism and broad clinical morbidity. Therefore, novel and more effective drugs are urgent needed for improvement of patients' quality of life. Glutamate receptors have been associated with the development of the central sensitization of chronic pain. Inhibition of N-methyl-d-aspartate (NMDA) and metabotropic glutamate (mGlu) receptors can effectively attenuate bone cancer pain, respectively. Herein, our results indicated that levo-Corydalmine (l-CDL), a compound from Corydalis yanhusuo W.T. Wang, which has been used in traditional Chinese medicine for pain relief could effectively attenuate bone cancer pain induced by tibia bone cavity tumor cell implantation (TCI) through simultaneously inhibiting the NMDA and mGlu1/5 receptors in rat spinal cord without notable side effects. Both intragastric and intrathecal administration of l-CDL significantly alleviated the mechanical hypersensitivity induced by TCI in rats, and the analgesic effect of l-CDL could be reversed by intrathecal administration of NMDA receptor agonist NMDA and mGlu1/5 receptor agonist DHPG but not AMPA receptor agonist AMPA. l-CDL could also selectively suppress NMDA and DHPG induced rapid rise in Ca 2+ oscillations in primary cultures neurons of spinal cord in vitro. The antinociception of l-CDL were partially mediated by the reduced phosphorylation of PKC γ and ERK1/2 in spinal cord of TCI rats in a NMDA and mGlu1/5 dependent manner. In conclusion, these results suggested that l-CDL attenuates TCI induced bone cancer pain through simultaneously inhibiting the NMDA and mGlu1/5 receptors and the downstream PKC γ, ERK1/2 signaling pathways in the spinal cord., (© 2017 UICC.)

Purpose: To use meta-analysis techniques to evaluate the efficacy and safety of platelet-rich plasma (PRP) injections for the treatment knee of osteoarthritis (OA)., Methods: We performed a systematic literature search in PubMed, Embase, Scopus, and the Cochrane database through April 2016 to identify Level I randomized controlled trials that evaluated the clinical efficacy of PRP versus control treatments for knee OA. The primary outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores. The primary outcomes were compared with their minimum clinically important differences (MCID)-defined as the smallest difference perceived as important by the average patient., Results: We included 10 randomized controlled trials with a total of 1069 patients. Our analysis showed that at 6 months postinjection, PRP and hyaluronic acid (HA) had similar effects with respect to pain relief (WOMAC pain score) and functional improvement (WOMAC function score, WOMAC total score, International Knee Documentation Committee score, Lequesne score). At 12 months postinjection, however, PRP was associated with significantly better pain relief (WOMAC pain score, mean difference -2.83, 95% confidence interval [CI] -4.26 to -1.39, P = .0001) and functional improvement (WOMAC function score, mean difference -12.53, 95% CI -14.58 to -10.47, P  < .00001; WOMAC total score, International Knee Documentation Committee score, Lequesne score, standardized mean difference 1.05, 95% CI 0.21-1.89, P = .01) than HA, and the effect sizes of WOMAC pain and function scores at 12 months exceeded the MCID (-0.79 for WOMAC pain and -2.85 for WOMAC function score). Compared with saline, PRP was more effective for pain relief (WOMAC pain score) and functional improvement (WOMAC function score) at 6 months and 12 months postinjection, and the effect sizes of WOMAC pain and function scores at 6 months and 12 months exceeded the MCID. We also found that PRP did not increase the risk of adverse events compared with HA and saline., Conclusions: Current evidence indicates that, compared with HA and saline, intra-articular PRP injection may have more benefit in pain relief and functional improvement in patients with symptomatic knee OA at 1 year postinjection., Level of Evidence: Level I, meta-analysis of Level I studies., (Copyright © 2016. Published by Elsevier Inc.)