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Cheng-Feng Luo,1,2 Ning Hou,2,3 Juan Tian,1,2 Mu Yuan,2,3 Shi-Ming Liu,1,2 Long-Gen Xiong,1,2 Jian-Dong Luo,2,3 Min-Sheng Chen1,2,41The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China; 2Guangzhou Institute of Cardiovascular Disease, Guangzhou, People's Republic of China; 3Guangzhou Medical University, Guangzhou, People's Republic of China; 4Southern Medical University, Guangzhou, People's Republic of ChinaAbstract: Puerarin has multiple pharmacological effects and is widely prescribed for patients with cardiovascular diseases including hypertension, cerebral ischemia, myocardial ischemia, diabetes mellitus, and arteriosclerosis. We have successfully prepared puerarin-loaded solid lipid nanoparticles (Pue-SLNs) for oral administration. Pue-SLNs are prepared using monostearin, soya lecithin, and poloxamer 188. SLNs may alter the course of puerarin absorption predominantly to and through lymphatic routes and regions, presumably following a transcellular path of lipid absorption, especially by enterocytes and polar epithelial cells of the intestine. The alteration of absorption might influence the metabolic profile of puerarin when incorporated into SLNs. In the present study, we investigated the metabolic profile of puerarin in rat plasma and urine using rapid resolution liquid chromatography–tandem mass spectrometry after a single-dose intragastric administration of Pue-SLNs in comparison with puerarin suspension. Two glucuronidated metabolites of puerarin, puerarin-4΄-O-glucuronide and puerarin-7-O-glucuronide, were detected in rat plasma and urine after intragastric administration of Pue-SLNs, with the latter acting as the major metabolite. Similar results were found in rat plasma and urine after intragastric administration of puerarin suspension. The results suggest that incorporation of puerarin into SLNs does not change either the position of glucuronidation or the metabolic pathway of puerarin in rats.Keywords: puerarin, solid lipid nanoparticles, metabolic profiling

Tabanids, commonly known as horseflies and belonging to the family Tabanidae, are blood-feeding arthropods (BFA) found worldwide. They are known for their ability to mechanically and biologically transmit various animal pathogens. Tabanids are potential vectors for diseases such as Francisella tularensis, Anaplasma marginale, Theileria spp., and contributors to lumpy skin diseases. Despite their involvement in common BFA studies, tabanids have not been extensively explored in microbiome research. In this study, the microbiota structure and composition in various organs of four distinct genera of tabanids: Atylotus , Haematopota , Tabanus , and Hybomitra were examined. High-throughput sequencing of the bacterial 16S rRNA gene was performed to gain insights into the microbial communities associated with the different tabanid species. Result display that microbiota composition and diversity, including Firmicutes, Proteobacteria, and Bacteroidetes, varied significantly among the different organs, with the ovaries exhibiting significantly higher diversity. Apart from the Haematopota genus, Tenericutes were enriched in the midgut of other tabanid species, whereas the Malpighian tubules exhibited a higher abundance of Bacteroides. Notably, the ovarian microbiota structure was conserved among the four tabanid species, indicating its potential association with reproductive development. Evaluation of the potential pathogen risk revealed putative pathogens in over 100 genera associated with these tabanid commensal organisms. Twenty genera were annotated as zoonotic agents with a high abundance of Citrobacter and Brucella , highlighting the presence of this important group of zoonotic pathogens. Functional predictions of vector-microbiota interactions indicate that microbiota significantly affects vector biological traits and can influence pathogen transmission via direct interactions or by regulating host immunity and nutrition. For the first time, the distribution characteristics and functions of four genera of horsefly microbiota were analyzed, revealing the presence of multiple potential pathogenic microorganisms. These findings provide valuable insights for future research and the development of symbiotic-based strategies to control insect-borne diseases among tabanids., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qiu, Lv, Wang, Ju, Luo, Liu, Na, Chang and Jiang.)

Background: The purpose of this study was to perform a biomechanical analysis to compare different medial column fixation patterns for valgus pilon fractures in a case-based model., Methods: Based on the fracture mapping, 48 valgus pilon fracture models were produced and assigned into four groups with different medial column fixation patterns: no fixation (NF), K-wires (KW), intramedullary screws (IS), and locking compression plate (LCP). Each group contained wedge-in and wedge-out subgroups. After fixing each specimen on the machine, gradually increased axial compressive loads were applied with a load speed of one millimeter per minute. The maximum peak force was set at 1500 N. Load-displacement curves were generated and the axial stiffness was calculated. Five different loads of 200 N, 400 N, 600 N, 800 N, 1000 N were selected for analysis. The specimen failure was defined as resultant loading displacement over 3 mm., Results: For the wedge-out models, Group-IS showed less displacement (p < 0.001), higher axial stiffness (p < 0.01), and higher load to failure (p < 0.001) than Group-NF. Group-KW showed comparable displacement under loads of 200 N, 400 N and 600 N with both Group-IS and Group-LCP. For the wedge-in models, no statistical differences in displacement, axial stiffness, or load to failure were observed among the four groups. Overall, wedge-out models exhibited less axial stiffness than wedge-in models (all p < 0.01)., Conclusions: Functional reduction with stable fixation of the medial column is essential for the biomechanical stability of valgus pilon fractures and medial column fixation provides the enough biomechanical stability for this kind of fracture in the combination of anterolateral fixation. In detail, the K-wires can provide a provisional stability at an early stage. Intramedullary screws are strong enough to provide the medial column stability as a definitive fixation. In future, this technique can be recommended for medial column fixation as a complement for holistic stability in high-energy valgus pilon fractures., (© 2024. The Author(s).)

Background: Rickettsia and related diseases have been identified as significant global public health threats. This study involved comprehensive field and systematic investigations of various rickettsial organisms in Yunnan Province., Methods: Between May 18, 2011 and November 23, 2020, field investigations were conducted across 42 counties in Yunnan Province, China, encompassing small mammals, livestock, and ticks. Preliminary screenings for Rickettsiales involved amplifying the 16S rRNA genes, along with additional genus- or species-specific genes, which were subsequently confirmed through sequencing results. Sequence comparisons were carried out using the Basic Local Alignment Search Tool (BLAST). Phylogenetic relationships were analyzed using the default parameters in the Molecular Evolutionary Genetics Analysis (MEGA) program. The chi-squared test was used to assess the diversities and component ratios of rickettsial agents across various parameters., Results: A total of 7964 samples were collected from small mammals, livestock, and ticks through Yunnan Province and submitted for screening for rickettsial organisms. Sixteen rickettsial species from the genera Rickettsia, Anaplasma, Ehrlichia, Neoehrlichia, and Wolbachia were detected, with an overall prevalence of 14.72%. Among these, 11 species were identified as pathogens or potential pathogens to humans and livestock. Specifically, 10 rickettsial organisms were widely found in 42.11% (24 out of 57) of small mammal species. High prevalence was observed in Dremomys samples at 5.60%, in samples from regions with latitudes above 4000 m or alpine meadows, and in those obtained from Yuanmou County. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis were broadly infecting multiple genera of animal hosts. In contrast, the small mammal genera Neodon, Dremomys, Ochotona, Anourosorex, and Mus were carrying individually specific rickettsial agents, indicating host tropism. There were 13 rickettsial species detected in 57.14% (8 out of 14) of tick species, with the highest prevalence (37.07%) observed in the genus Rhipicephalus. Eight rickettsial species were identified in 2375 livestock samples. Notably, six new Rickettsiales variants/strains were discovered, and Candidatus Rickettsia longicornii was unambiguously identified., Conclusions: This large-scale survey provided further insight into the high genetic diversity and overall prevalence of emerging Rickettsiales within endemic hotspots in Yunnan Province. The potential threats posed by these emerging tick-borne Rickettsiales to public health warrant attention, underscoring the need for effective strategies to guide the prevention and control of emerging zoonotic diseases in China., (© 2024. The Author(s).)

Background: Graduate nursing education plays an important role in the development of an innovative nation. Such education benefits the health of the community by cultivating competent and highly skilled nurses who can provide safe and quality nursing care. The number of students pursuing nursing degrees in China is insufficient, to meet the social demand for advanced practice nurses. The part-time Master of Nursing Specialist program for students offers flexible learning options for working nurses. However, the relatively low level of learning engagement exhibited by this group has raised concerns among policy-makers and nursing educators. An in-depth study of the factors affecting the learning engagement of part-time Master of Nursing Specialist postgraduates, especially with regard to their combined effect, is expected to provide a basis for improving the level of learning engagement among such students., Methods: This study used ability-motivation-opportunity-theory and fuzzy-set qualitative comparative analysis to analyze the relationships between five conditions (i.e., supportive campus environment, supportive work environment, student-faculty interaction, research motivation and time management ability) and learning engagement by reference to data collected from a sample of 225 part-time Master of Nursing Specialist students who were enrolled in China., Results: The fuzzy-set qualitative comparative analysis results indicated that individual examples of these antecedent conditions were insufficient to influence learning engagement. In contrast, three combinations of the five conditions led to high levels of learning engagement, and substitutability and complementarity were observed among the various elements in the configuration., Conclusions: Research motivation, student-faculty interaction, a supportive work environment and time management are factors that can influence part-time postgraduates' learning engagement. Supervisors can enhance their research skills and expertise, hospitals can establish supportive environments for students, and students can strengthen their research motivation and time management abilities., Competing Interests: Declaration of competing interest Authors declare have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Sclerotherapy is purportedly less effective in patients with hemorrhagic than with non-hemorrhagic lymphatic malformations (LMs). We aimed to compare the efficacy of bleomycin-lauromacrogol foam (BLF) sclerotherapy in the treatment of macrocystic LMs with and without intralesional hemorrhage., Methods: Fifty-five children with macrocystic LMs admitted to the Pediatric Surgery Department were retrospectively included. The patients were allocated into a hemorrhage group (23 cases) or a non-hemorrhage group (32 cases) based on the occurrence of an intracapsular hemorrhage. The diagnosis was confirmed by physical examination, color ultrasound, magnetic resonance imaging, and puncture findings. BLF was injected into the capsule after draining the cystic fluid under color ultrasound guidance. Patients whose lesions were unchanged or showed minor change after 1 month were treated again using the same method. Changes in lesion size and the number of treatments were recorded. Effectiveness was classified as excellent (volume reduction ≥90%), good (50%≤volume reduction<90%), or poor (volume reduction <50%)., Results: In the hemorrhage group, 17, 6, and 0 patients' outcomes were classified as excellent, good, and poor, respectively. The overall efficacy rate was 100%. In the non-hemorrhage group, 23, 7, and 2 patients' outcomes were classified as excellent, good, and poor, respectively. The overall efficacy rate was 93.8%. There was no significant difference in efficacy rate between groups (P = 0.767)., Conclusions: BLF is an effective and safe treatment for macrocystic LMs with bleeding. The results were similar in patients with and without bleeding., Level of Evidence: Treatment, Level III., Competing Interests: Conflicts of interest There are no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation., Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA,  flaB  and  glpQ  genome were analyzed and phylogenetic trees were constructed., Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis , H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri -like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings., Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen., Competing Interests: The authors declare no competing interests., (© 2024 The Authors. Published by Elsevier B.V.)

Rosuvastatin (RSV) is widely used to treat hyperlipidemia and hypercholesterolemia and is recommended for the primary and secondary prevention of cardiovascular diseases (CVD). In this study, we aimed to explore its action and mechanism in lung adenocarcinoma (LUAD) therapy. Lewis and CMT64 cell-based murine subcutaneous LUAD models were employed to explore the effects of RSV monotherapy combined with cisplatin and gemcitabine. Human lung fibroblasts and human LUAD cell lines were used to assess the effects of RSV on normal and LUAD cells. Bioinformatics and RNA interference were used to observe the contribution of cyclin A2 (CCNA2) knockdown to RSV inhibition and to improve chemosensitivity in LUAD. RSV significantly suppressed grafted tumor growth in a murine subcutaneous LUAD model and exhibited synergistic anti-tumor activity with cisplatin and gemcitabine. In vitro and in vivo experiments demonstrated that RSV impaired the proliferation and migration of cancer cells while showing little inhibition of normal lung cells. RNA interference and CCK8 detection preliminarily indicated that RSV inhibited tumor growth and enhanced the chemosensitivity to cisplatin and gemcitabine by downregulating CCNA2. RSV suppressed LUAD progression and enhanced chemosensitivity to cisplatin and gemcitabine by downregulating CCNA2, which should be prior consideration for the treatment of LUAD, especially for patients co-diagnosed with hyperlipidemia and hypercholesterolemia.

Generating diverse ferroelectric ice nanotubes (NTs) efficiently has always been challenging, but matters in nanomaterial synthesis and processing technology. In the present work, we propose a method of growing ice NT forests in a single cooling process. A three-dimensional (3D) graphene structure was selected to behave as a representative container in which a batch of (5, 0) ice NTs was formed simultaneously under the cooling process from molecular dynamics simulation. Other similar 3D graphene structures but with different hole configurations, like uniform triangle or both triangle and pentagon, were also tested, revealing that ice NTs with different tube indices, i.e. both (3, 0) and (5, 0), could also be formed at the same time. Intriguingly, the orientations of the dipole moments of the water molecules of an ice NT formed were independent of each other, making the net ferroelectricity of the whole system weakened or even cancelled. An electric field could help change the orientation of the water molecules of the already obtained ice NTs and even twist the tube to be a spiral (5, 1) one if it was applied during the cooling process, such that the net ferroelectricity was greatly improved. The underlying physical mechanism of all phase transition phenomena, including the improvement of the ferroelectricity under an electric field, were explored in depth from the phase transition curves and structural point of view. The obtained results are of significant application value for improving the preparation efficiency of nano-ferroelectric materials, which are prosperous in nano-devices.

Purpose: The biomechanical capacity of "Barrel Hoop Plate (BHP)" in the treatment of the posterolateral tibial plateau (PL) depression fractures remains unknown. In this study, two kinds of posterolateral tibial plateau depression models involving mild slope-type depression fracture (MSDF) and local sink hole-type depression fracture (LSDF) were created to test and compare the biomechanical capacities of BHP with the other two conventional fixations (Anterolateral Plate and Posterolateral Plate, ALP and PLP) by finite element analysis., Methods: The 3D models of three kinds of plate-screw systems and the two kinds of PL-depression models (MSDF and LSDF) were created. An axial force of 400N was applied from the distal femur to the tibial plateau. The maximal displacements of the posterolateral fractures (PLFs), the distribution on the PLFs articular surface and key points displacements were measured. Stresses in the fixation complex including the maximal Equivalent (von-Mises) Stress of implants, the max shear stress of PLFs and stiffness of the fixation were calculated., Results: The maximal displacement of MSDF was least in Group BHP. The maximal displacement of LSDF was least in Group ALP. In MSDF, BHP showed the best rim fix effect in MSDF, but unsatisfactory results in LSDF. In both MSDF and LSDF, the greatest max Equivalent Stress of the plate and the screw occurred in the PLP system. ALP and BHP showed a comparable stiffness in MSDF and ALP had the strongest stiffness in the fixation of LSDF., Conclusions: In MSDF, the BHP has the best biomechanical capacity, especially in displacements of key points such as the PL rim, fracture line, and depression center. In LSDF, the ALP system shows the best biomechanical effect. Although the PLP has the best fixation effect on the posterior wall, it is not suitable for PL-depression fracture fixation., (© 2023. The Author(s).)

Background: Clinical observations suggest a complex relationship between obesity and coronary artery disease (CAD). This study aimed to characterize the intermediate metabolism phenotypes among obese patients with CAD and without CAD., Methods: Sixty-two participants who consecutively underwent coronary angiography were enrolled in the discovery cohort. Transcriptional and untargeted metabolomics analyses were carried out to screen for key molecular changes between obese patients with CAD (CAD obese), without CAD (Non-CAD obese), and Non-CAD leans. A targeted GC-MS metabolomics approach was used to further identify differentially expressed metabolites in the validation cohorts. Regression and receiver operator curve analysis were performed to validate the risk model., Results: We found common aberrantly expressed pathways both at the transcriptional and metabolomics levels. These pathways included cysteine and methionine metabolism and arginine and proline metabolism. Untargeted metabolomics revealed that S-adenosylhomocysteine (SAH), 3-hydroxybenzoic acid, 2-hydroxyhippuric acid, nicotinuric acid, and 2-arachidonoyl glycerol were significantly elevated in the CAD obese group compared to the other two groups. In the validation study, targeted cysteine and methionine metabolomics analyses showed that homocysteine (Hcy), SAH, and choline were significantly increased in the CAD obese group compared with the Non-CAD obese group, while betaine, 5-methylpropanedioic acid, S-adenosylmethionine, 4-PA, and vitamin B2 (VB2) showed no significant differences. Multivariate analyses showed that Hcy was an independent predictor of obesity with CAD (hazard ratio 1.7; 95%CI 1.2-2.6). The area under the curve based on the Hcy metabolomic (HCY-Mtb) index was 0.819, and up to 0.877 for the HCY-Mtb.index plus clinical variables., Conclusion: This is the first study to propose that obesity with hyperhomocysteinemia is a useful intermediate metabolism phenotype that could be used to identify obese patients at high risk for developing CAD., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: This study aimed to evaluate the clinical outcomes of ipsilateral femoral neck and shaft fractures and identify the risk factors associated with missed diagnosis of femoral neck fractures and clinical outcomes of this fracture., Methods: The ipsilateral femoral neck and shaft fractures from seven centers were retrospectively reviewed. Data on injury mechanism, fracture pattern, and fracture classification; surgical factors including fixation method; and timing of detection of femoral neck fracture were analyzed. The clinical outcomes, complications, and the incidence of avascular necrosis of the femoral head (AVNFH) were reviewed. Risk factors for missed femoral neck fracture and complications were analyzed., Results: In total, 74 patients with an average age of 43.6 years were included. Of the femoral shaft fractures, 56.8% were type A, 21.6% were type B, and 21.6% were type C. Sixteen patients had an open fracture of the femoral shaft. Femoral neck fracture was initially missed in 27% patients and the timing of delayed diagnosis was at an average of 11.1 days after injury. For detecting femoral neck fractures, minimal displacement of the femoral neck fracture was a risk factor, whereas computed tomography (CT) was a protective factor. The incidence of AVNFH was 6.8% at an average of 36.8 months after injury. The AVNFH group had more displaced femoral neck fractures at the time of surgery, but there was no difference in the timing of diagnosis compared to non-AVNFH group. The femoral shaft showed considerable healing problems, with an average union time of 29.7 weeks and a 20.2% nonunion rate., Conclusion: Ipsilateral femoral neck and shaft fractures had a high rate of missed diagnosis, especially in minimally displaced fractures; however, CT was a protective factor. AVNFH occurred in 6.8% and was related to femoral neck fracture displacement, but not delayed diagnosis. The femur nonunion rate was high, which warrants attention., Competing Interests: Declaration of competing interest Authors hereby certify that they have no conflicts of interest to declare in connection with this study., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Intussusception can be managed by pneumatic reduction, ultrasound-guided hydrostatic reduction, open or laparoscopic surgery, but laparoscopy in such cases remains controversial., Aim: To explore the clinical characteristics, effectiveness, and complications of surgical reduction for intussusception using laparoscopy in children., Methods: This study was a retrospective case series of pediatric patients with intussusception who underwent surgical reduction by laparoscopy from May 2011 to April 2016 at Taizhou Hospital of Zhejiang Province. Clinical characteristics (operation time, intraoperative blood loss, conversion rate of laparotomy, reasons for conversion, postoperative hospital stay, and adverse events) were described., Results: The 65 patients included 45 boys and 20 girls. The average age was 2.3 years (27.5 ± 24.5 mo). Of the 65 patients, 61 underwent surgical reduction by laparoscopy after a failed enema reduction of intussusception, and four underwent the procedure directly. All patients were treated successfully and 57 (87.7%) patients underwent successful laparoscopic surgery, two of which had a spontaneous reduction. Among the remaining cases, one was converted to open surgery via right upper quadrant incision, and seven required enlarged umbilical incisions. Intestinal resection was performed in 5 patients because of abnormal bowel lesions. There were no complications (intestinal perforations, wound infections, or intestinal adhesions) during the follow-up of 3 years to 8 years. Two patients experienced a recurrence of intussusception; one was resolved with pneumatic reduction, and the other underwent a second laparoscopic surgery., Conclusion: Laparoscopic approach for pediatric intussusception is feasible and safe. Bowel resection if required can be performed by extending umbilical incision without the conventional laparotomy., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: Investigate if azilsartan protects against myocardial hypertrophy by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated pathways., Methods: Abdominal aortic constriction (AAC)-induced cardiac hypertrophy in rats was applied. Azilsartan or vehicle was administered daily for 6 weeks in sham or AAC rats. Cardiac morphology and ventricular function were determined. Azilsartan effects upon neonatal rat cardiomyocyte (NRCM) hypertrophy and molecular mechanisms were studied in angiotensin (Ang) II-stimulated NRCMs in vitro. Nrf2-small interfering RNA (siRNA) was used to knockdown Nrf2 expression. Messenger RNA (mRNA)/protein expression of Kelch-like erythroid cell-derived protein (Keap)1 and Nrf2 and its downstream antioxidant enzymes was determined by real-time reverse transcription-quantitative polymerase chain reaction and western blotting, respectively., Key Findings: Azilsartan treatment ameliorated cardiac hypertrophy/fibrosis significantly in AAC rats. Azilsartan increased expression of Nrf2 protein but decreased expression of Keap1 protein. Upregulation of protein expression of Nrf2's downstream antioxidant enzymes by azilsartan treatment was observed. Azilsartan inhibited Ang II-induced NRCM hypertrophy significantly and similar effects on the Keap1-Nrf2 pathway were observed in vivo. Nrf2 knockdown markedly counteracted the beneficial effects of azilsartan on NRCM hypertrophy and the Keap1-Nrf2 pathway., Conclusions: Azilsartan restrained pressure overload-induced cardiac remodelling by activating the Keap1-Nrf2 pathway and increasing expression of downstream antioxidant enzymes to alleviate oxidative stress., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To investigate the effects of aspirin-omitted dual antithrombotic therapy (DAT) on myocardial infarction and stent thrombosis in non-valvular atrial fibrillation (NVAF) patients presenting with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI)., Methods and Results: A systematic review and meta-analysis were performed using PubMed to search for randomized clinical trials comparing DAT with triple antithrombotic therapy (TAT) in this setting. Three trials involving 8845 patients were included (4802 and 4043 patients treated with DAT and TAT, respectively). There were no significant differences in all-cause death and stroke between the aspirin-omitted DAT group and TAT group. Otherwise, the incidence of myocardial infarction was significantly higher with aspirin-omitted DAT vs. TAT [odds ratio (OR): 1.29, 95% confidence interval (CI): 1.02-1.63; P = 0.04; I2 = 0%]. Similarly, the incidence of stent thrombosis increased in patients treated with aspirin-omitted DAT vs. TAT (OR: 1.61, 95% CI: 1.02-2.53; P = 0.04; I2 = 0%). The occurrence of major bleeding and clinically relevant non-major bleeding events, as defined by the International Society on Thrombosis and Haemostasis, was significantly lower with aspirin-omitted DAT vs. TAT (OR: 0.61, 95% CI: 0.48-0.78; P = 0.02; I2 = 76%). Similar results were found according to the International Society on Thrombosis and Haemostasis major bleeding, Thrombolysis in Myocardial Infarction major or minor bleeding, and Thrombolysis in Myocardial Infarction major bleeding scales., Conclusion: Aspirin-omitted DAT reduces the occurrence of bleeding episodes, with a higher rate of myocardial infarction and stent thrombosis in NVAF patients presenting with ACS or undergoing PCI., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Introduction: The relationship between patient expectations and clinical outcomes has recently been of increasing interest in the field of orthopaedics. The objective of this study was to evaluate the relationships between (1) patient pre-treatment expectations and post-treatment clinical outcomes, and (2) fulfillment of expectations and patient satisfaction, following distal radius fracture., Methods: This was a prospective multicenter cohort study conducted across three hospitals. A total of 133 patients admitted to hospital between 2016 and 2018 with a distal radius fracture were recruited. Patients were administered the Trauma Expectation Factor (TEF) at baseline to measure expectations of pain and functioning at one-year post-injury. Patients were followed up at 6 and 12 months post-injury and outcomes were measured using the Trauma Outcome Measure (TOM), Shortened Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire, and Short-Form 12-item (SF-12) health survey. Fulfillment of expectations was measured as TEF score minus TOM score at each time point. Patient satisfaction was also measured using the Patient Satisfaction Questionnaire Short Form (PSQ-18). Multivariate regression models were created to evaluate the effect of expectations on outcomes., Results: Patient expectations correlated moderately with outcomes at 6 and 12 months post-injury. In the multivariate analysis, patient expectations were predictive of better outcomes at 6 and 12 months. Injury severity, age, mechanism of injury, and whether the injury occurred on duty also contributed significantly to one or more regression models. Patient satisfaction correlated weakly with fulfillment of expectations at 6 months, but moderately with all outcome scores. At 12 months, satisfaction did not correlate significantly with expectations fulfillment but correlated moderately to highly with all outcome scores., Conclusion: Patient expectations independently predicted outcomes at 6 and 12 months post-injury. Standardized assessment and management of patient expectations may be relevant to future clinical practice and research to best quantify and optimize patient outcomes., Competing Interests: Declarations 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 © 2020. Published by Elsevier Ltd.)

To aim of the present paper was to introduce a novel fixation technique for the treatment of inferior pole fracture of the patella. We performed a prospective observational study of consecutive cases of inferior pole fracture of the patella that were treated at our institution between January 2018 and June 2019. The patients include three men and one woman, with an average age of 47 years (range: 42-59 years). All patients were treated with the novel rim plating fixation technique for preserving the inferior pole of the patella. During the surgery, a 2.4 mm straight locking compression plate was contoured to adapt to the arc of the lower half of the patella as the rim plate. After reduction of the fracture, the rim plate was fixed to the proximal fragment of the patella through multiple locking screws, against the continuous pull of the patellar tendon. The rim plate encircles and constricts the inferior pole fragments, functioning as a compression and blocking construct. If necessary, an additional anterior tension band or mini locking plate can be used to further prevent anterior displacement of the inferior pole fragments. Under this rigid fixation, motion of the knee and full weight-bearing were encouraged postoperatively. The patients were followed up monthly until 12 months after surgery. The time to achieve 90°pain-free, full range of motion of the knee, and fracture healing, were recorded. Related complications were monitored, including infection, loss of reduction, fixation failure, anterior knee pain, and soft-tissue irritation. The modified Cincinnati knee rating system was used for knee function assessment. The average operative time was 58.8 min (range: 52-63 min). The average blood loss was 59.8 mL (range: 45-71 mL). For all patients, pain-free 90° range of motion was restored in 2-4 weeks, and the full range of motion was restored in 8-11 weeks. All patients achieved bone union in 6-9 weeks with no displacement of the fragments or breakage of the implant. No patient complained of anterior knee pain or soft-tissue irritation. The modified Cincinnati score at 12-month follow up demonstrated excellent outcomes in all four patients. The rim plating technique may be a feasible option for the treatment of the inferior pole fracture of the patella., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Purpose: To investigate miR-99a expression and its effect on proliferation of oral squamous cell carcinoma (OSCC)., Methods: miRNA microarrays associated with OSCC were identified in GEO database. The expression levels of miR-99a were detected in 63 OSCC tissues and adjacent normal tissues and cell lines. The relationship between clinicopathological parameters and miR-99a expression was analyzed by using ANOVA analysis. The ability of cell growth and clone formation were examined in SCC9 and SCC25 cells transfected with miR-99a mimics. The target genes of miR-99a were predicted by Targetscan software. There resulting data were analyzed using SPSS 19.0 software package., Results: The differently expressed miRNAs were analyzed based on GSE103931 microarray. miR-99a was significantly downregulated in OSCC tissues and cell lines. miR-99a expression was significantly associated with T stage, pathological grading and patients' prognosis. miR-99a overexpression inhibited OSCC cell proliferation and clone formation, while miR-99a inhibition contributed to decreased proliferation and clone formation ability. In addition, miR-99a combined with mTOR gene's 3'UTR was negatively correlated with mTOR expression in OSCC tissues., Conclusions: miR-99a functions as a tumor suppressor in OSCC and inhibits OSCC cell proliferation by targeting mTOR.

Estrogen deficiency induces cardiac dysfunction and increases the risk of cardiovascular disease in postmenopausal women and in those who underwent bilateral oophorectomy. Previous evidence suggests that puerarin, a phytoestrogen, exerts beneficial effects on cardiac function in patients with cardiac hypertrophy. In this study, we investigated whether puerarin could prevent cardiac hypertrophy and remodeling in ovariectomized, aortic-banded rats. Female SD rats subjected to bilateral ovariectomy (OVX) plus abdominal aortic constriction (AAC). The rats were treated with puerarin (50 mg·kg -1  ·d -1 , ip) for 8 weeks. Then echocardiography was assessed, and the rats were sacrificed, their heart tissues were extracted and allocated for further experiments. We showed that puerarin administration significantly attenuated cardiac hypertrophy and remodeling in AAC-treated OVX rats, which could be attributed to activation of PPARα/PPARγ coactivator-1 (PGC-1) pathway. Puerarin administration significantly increased the expression of estrogen-related receptor α, nuclear respiratory factor 1, and mitochondrial transcription factor A in hearts. Moreover, puerarin administration regulated the expression of metabolic genes in AAC-treated OVX rats. Hypertrophic changes could be induced in neonatal rat cardiomyocytes (NRCM) in vitro by treatment with angiotensin II (Ang II, 1 μM), which was attenuated by co-treatemnt with puerarin (100 μM). We further showed that puerarin decreased Ang II-induced accumulation of non-esterified fatty acids (NEFAs) and deletion of ATP, attenuated the Ang II-induced dissipation of the mitochondrial membrane potential, and improved the mitochondrial dysfunction in NRCM. Furthermore, addition of PPARα antagonist GW6471 (10 μM) partially abolished the anti-hypertrophic effects and metabolic effects of puerarin in NRCM. In conclusion, puerarin prevents cardiac hypertrophy in AAC-treated OVX rats through activation of PPARα/PGC-1 pathway and regulation of energy metabolism remodeling. This may provide a new approach to prevent the development of heart failure in postmenopausal women.

Background: Laparoscopic pyloromyotomy has become a gold standard for the treatment of congenital hypertrophic pyloric stenosis (HPS). There have been recent reports on the use of transumbilical single-site laparoscopic surgery for congenital HPS; however, using transumbilical single-site laparoscopic surgery in pediatric cases is still controversial due to the difficulty with manipulation. In this study, some preliminary experience with the application of a novel transumbilical single-site laparoscopic approach in congenital HPS is described. Methods: A retrospective study was conducted involving 25 patients with congenital HPS treated in our hospital from August 2016 to August 2019. A pyloric electrocoagulation chisel combined with a left-handed main operation was completed in all of the patients and the operative times, postoperative length of stay, and operative complications were recorded. Results: The laparoscopic operation was completed in 25 patients with an average operative time of 21.9 ± 5.5 minutes, average postoperative length of stay of 2.5 ± 0.9 days, and no perforations of the pyloric mucosa, recurrent obstruction, surgical incision infections, and incision hernias. All of the patients had at least 3 months of follow-up, good growth and development, and the parents were satisfied with the postoperative scars. Conclusion: A pyloric electrocoagulation chisel combined with a left-handed main operation in the treatment of congenital HPS by a single-site umbilical laparoscopic pyloromyotomy is safe and effective, and can achieve a satisfactory cosmetic effect.

Objectives: The purpose of our study is to evaluate the three-dimensional biomechanical properties of "Barrel Hoop plate" in two kinds of artificial posterolateral tibial plateau fracture fragment (PLF) by using of synthetic models, each of which has an initial amplifying displacement tendency., Material and Methods: Thirty-six tibiae models were randomly assigned into two groups with different displacement tendencies: posterior displacement (PD) and lateral displacement (LD). Each model was then fixed with three patterns: Anterolateral plate (AP), Posterolateral plate (PP), and "Barrel Hoop plate" (BHP). Displacement in three axes of vertical, sagittal and horizontal axis was captured by Optotrak Certus motion analysis system. Bluehill 2 software was used for load control and data collection., Results: In Model-PD, when the load was over 1000 N, the posterior displacement of Group-PP and Group-BHP were less than Group-AP (P<0.01). The inferior displacement in the vertical axis of Group-PP was larger than both Group-AP and Group-BHP in all the loading set (P<0.01). In Model-LD, both of the lateral displacement in Group-AP and Group-BHP was less than that of Group-PP when the load was over 1000 N (P<0.01). The inferior displacement of Group-AP was less than that of Group-PP in the load of 1500 N (P<0.01). Both of the posterior displacement of Group-AP and Group-BHP was less than that of Group-PP when the loading was 1500 N (P<0.01). The stiffness of Group PP was less than that of Group AP (P<0.01)., Conclusions: The results demonstrated that the 2.7 mm "Barrel Hoop plate" had a greater capacity of anti-three-dimension axes displacement of PLF. The 3.5 mm Anterolateral plate had the advantage in anti-lateral displacement and anti-inferior displacement but was weak at anti-posterior displacement of PLF. The 2.7 mm Posterolateral plate was stronger in anti-posterior, however, weak in anti-inferior displacement capacity., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The unique extracellular electron transfer (EET) ability has positioned electroactive bacteria (EAB) as a major class of cellular chassis for genetic engineering aimed at favorable environmental, energy, and geoscience applications. However, previous efforts to genetically enhance EET ability have often impaired the basal metabolism and cellular growth due to the competition for the limited cellular resource. Here, we design a quorum sensing-based population-state decision (PSD) system for intelligently reprogramming the EET regulation system, which allows the rebalanced allocation of the cellular resource upon the bacterial growth state. We demonstrate that the electron output from Shewanella oneidensis MR-1 could be greatly enhanced by the PSD system via shifting the dominant metabolic flux from initial bacterial growth to subsequent EET enhancement (i.e., after reaching a certain population-state threshold). The strain engineered with this system achieved up to 4.8-fold EET enhancement and exhibited a substantially improved pollutant reduction ability, increasing the reduction efficiencies of methyl orange and hexavalent chromium by 18.8- and 5.5-fold, respectively. Moreover, the PSD system outcompeted the constant expression system in managing EET enhancement, resulting in considerably enhanced electron output and pollutant bioreduction capability. The PSD system provides a powerful tool for intelligently managing extracellular electron transfer and may inspire the development of new-generation smart bioelectrical devices for various applications., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Background: The Trauma Expectation Factor Trauma Outcomes Measure (TEFTOM) questionnaire is a self-administered, patient-rated outcome measurement questionnaire designed to measure both 'expectation' and 'outcome' in orthopaedic trauma patients using two subsets of 10 items. We aimed to validate this instrument in a culturally diverse cohort of patients recruited from Asian and European regions., Methods: A total of 193 adult patients with surgically treated AO Foundation/Orthopaedic Trauma Association types 43 and 44 ankle malleolar and distal tibia fractures were recruited with 158 followed up till 1 year. Expectations were assessed prior to surgery, at 2 weeks and after 6 months using the trauma expectation factor (TEF) score. Outcomes were evaluated at 2 weeks, 6 and 12 months using the trauma outcome measure (TOM), American Academy of Orthopaedic Surgeons (AAOS), foot and ankle outcome score (FAOS) and short form-36 (SF-36) questionnaires. Psychometric properties of TEFTOM were assessed., Results: TEF and TOM demonstrated good internal consistency (Cronbach's α > 0.87) and reliability at all time points (intra-class correlation coefficients > 0.90). TOM showed strong correlations ( R 2 ≥ 0.60) with the AAOS foot and ankle score, all FAOS subscales, except 'symptoms' and SF-36 physical functioning, role physical, bodily pain, social functioning and the physical component summary at 6 and 12 months. Effect sizes for TOM were 2.30 and 0.74 from 2 weeks to 6 months and from 6 months to 12 months, respectively. The baseline patient TEF was predictive for the 1-year TOM score., Conclusions: TEFTOM demonstrated good psychometric properties in this cohort of patients with ankle fractures. The TEF 'expectation' score was predictive of the TOM 'outcome' score. We recommend researchers and clinicians to utilize TEFTOM when patient expectation measurement is concerned for orthopaedic trauma patients.

Objectives: CT-based three-column classification (TCC) has been widely used in the treatment of tibial plateau fractures (TPFs). In its updated version (updated three-column concept, uTCC), a fracture morphology-based injury mechanism was proposed for effective treatment guidance. In this study, the injury mechanism of TPFs is further explained, and its inter- and intraobserver reliability is evaluated to perfect the uTCC., Methods: The radiological images of 90 consecutive TPF patients were collected. A total of 47 men (52.2%) and 43 women (47.8%) with a mean age of 49.8 years (sd 12.4; 17 to 77) were enrolled in our study. Among them, 57 fractures were on the left side (63.3%) and 33 were on the right side (36.7%); no bilateral fracture existed. Four observers were chosen to classify or estimate independently these randomized cases according to the Schatzker classification, TCC, and injury mechanism. With two rounds of evaluation, the kappa values were calculated to estimate the inter- and intrareliability., Results: The overall inter- and intraobserver agreements of the injury mechanism were substantial (κ inter = 0.699, κ intra = 0.749, respectively). The initial position and the force direction, which are two components of the injury mechanism, had substantial agreement for both inter-reliability or intrareliability. The inter- and intraobserver agreements were lower in high-energy fractures (Schatzker types IV to VI; κ inter = 0.605, κ intra = 0.721) compared with low-energy fractures (Schatzker types I to III; κ inter = 0.81, κ intra = 0.832). The inter- and intraobserver agreements were relatively higher in one-column fractures (κ inter = 0.759, κ intra = 0.801) compared with two-column and three-column fractures., Conclusion: The complete theory of injury mechanism of TPFs was first put forward to make the TCC consummate. It demonstrates substantial inter- and intraobserver agreement generally. Furthermore, the injury mechanism can be promoted clinically. Cite this article : B-B. Zhang, H. Sun, Y. Zhan, Q-F. He, Y. Zhu, Y-K. Wang, C-F. Luo. Reliability and repeatability of tibial plateau fracture assessment with an injury mechanism-based concept. Bone Joint Res 2019;8:357-366. DOI: 10.1302/2046-3758.88.BJR-2018-0331.R1.

Background: The cardiovascular (CV) safety in terms of heart failure among different classes of treatment remains largely unknown. We sought to assess the comparative effect of these agents on heart failure outcomes., Methods: This study was registered in the International Prospective Register of Systematic Reviews (CRD 42016042063). MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials were searched. For the primary outcomes reported previously, studies between Jan 1, 1980 and June 30, 2016 were screened, and subsequently updated till Jan 24, 2019. We performed network meta-analysis to obtain estimates for the outcomes of heart failure, in particular by rankograms for ranking of heart failure risk as well as by pairwise comparisons among all classes of anti-diabetic medications., Results: A total of 91 trials were included, among which were 171,253 participants and 4163 reported cases of heart failure events. As for rankograms, the surface under the cumulative ranking curves (SUCRA) of sodium-glucose co-transporters 2 and thiazolidinediones were 93.4% and 4.3%, respectively, signifying the lowest and highest risk of heart failure, respectively. As for pairwise comparisons in the network, sodium-glucose co-transporters 2 were significantly superior to insulin (OR: 0.75, 95% CI 0.62-0.91), dipeptidyl peptidase 4 inhibitors (OR: 0.68, 95% CI 0.59-0.78), glucagon-like peptide-1 receptor agonists (OR: 0.65, 95% CI 0.54-0.78), and thiazolidinediones (OR: 0.46, 95% CI 0.27-0.77) in terms of heart failure risk. Furthermore, in an exploratory analysis among subjects with underlying heart failure or at risk of heart failure, the superiority of sodium-glucose co-transporters 2 was still significant., Conclusions: In terms of heart failure risk, sodium-glucose co-transporters 2 were the most favorable option among all classes of anti-diabetic medications.

Purpose: Intramedullary nailing (IMN) is a popular method in the management of femoral shaft fractures (FSFs). However, whether the association of IMN with pulmonary fat emboli can compromise the pulmonary and nervous systems is debatable. The purpose of this study is to compare IMN with the locked dual plating (LDP) method by assessing the clinical outcomes of FSF patients with head or chest injury., Method: A total of 126 FSF patients were included in this study between January 2010 and July 2016 and divided into LDP and IMN groups. Patient demographic characteristics, operative time, blood loss, Harris Hip Score, Lysholm Knee Score, radiological outcomes, and systemic complications were collected and compared between the two treatment groups. Patients were followed up for at least 12 months., Results: The LDP group performed better than IMN in terms of operative time, estimated blood loss amount, and malunion rate. Differences in function scores, fracture union rate, overall pulmonary complication rate, and in-hospital mortality between the two groups were not significant. Average radiographic union time was significantly longer in the LDP group (36.3 weeks) than in the IMN group (32.5 weeks). One case of fixation failure occurred postoperatively in the LDP group, whereas one case of fracture nonunion took place in the IMN group., Conclusion: Our findings suggest that dual-plating fixation is a promising method for FSFs with multiple injuries. However, the retrospective nature of this study necessitates high-quality trials to be performed to assess the clinical efficiency of dual plating.

Objective: The feasibility and perspective of pyloric chisel were discussed through the comparison of pyloric chisel and knife in the treatment of hypertrophic pyloric stenosis (HPS) in single-site umbilical laparoscopic pyloromyotomy (SSULP)., Methods: Fifty-eight cases of HPS treated in our hospital from February 2011 to March 2016 were retrospectively analyzed, in which 30 patients underwent pyloric chisel (Pyloric chisel Group) and 28 patients underwent knife (Knife Group). Operative time, estimated blood loss, and complications between the two groups were analyzed., Results: The operative time was shorter in Pyloric chisel Group than Knife Group (P < .05). The estimated blood loss was lower in Pyloric chisel Group than Knife Group (P < .05). The complication was less in Pyloric chisel Group than Knife Group (P < .05). There were 2 cases of mucosal perforations requiring conversions to open in Knife Group. Five cases of serous tearing occurred in the Knife Group. There was 1 case of serous tearing in the Pyloric chisel Group. All patients were followed up for 3 months, and there was no distinct scar in the umbilical., Conclusions: Patients were satisfied with no distinct scars in abdominal wall by pyloric chisel or knife to treat HPS in SSULP, but pyloric chisel is more effective and safer.

Objective: To present our clinical experience of treating varus malunion of the distal femur through a medial open-wedge osteotomy with double-plate fixation., Methods: A prospective cohort study was performed. From January 2005 to February 2015, 15 consecutive patients with varus malunion following distal femur fractures were surgically treated at a single level I trauma center. The coronal and sagittal deformity were corrected by a medial open-wedge osteotomy of the distal femur. A medial buttress plate was used to maintain the realignment. A lateral locking plate was additionally used as a protection plate. The mean age of patients at the time of the surgery was 35.5 years (range, 22-58 years). The radiographical evaluation included the mechanical femorotibial angle, the mechanical lateral distal femoral angle, the anatomic posterior distal femoral angle, and the leg length discrepancy. Clinical outcome evaluation consisted of the range of motion (ROM) and Hospital for Special Surgery (HSS) score., Results: Mean follow-up was 7.4 years (range, 4-11.5 years). Varus and flexion malalignment and limb discrepancy were adequately corrected in all patients. The mechanical femorotibial angle, the mechanical lateral distal femoral angle, and the anatomic posterior distal femoral angle were restored from 17.5° (range, 13°-25°) to 2.3° (range, - 2°-7°), 102.3° (range, 95°-112°) to 85.2° (range, 81°-92°), and 77.1° (range, 65°-87°) to 82.7° (range, 76°-88°), respectively. The leg length discrepancy was diminished from 3.4 cm (range, 2.4-4.5 cm) to 0.8 cm (range, 0-1.7 cm). The average bone healing time was 4.1 months (range, 2.5-6 months). The average ROM of the affected knees at 24-month follow-up was 3.4°-112.55°. The score of HSS at 4-years follow-up was 76.1 (range, 64-88). No internal fixation failure or secondary operation was noted until the last follow-up., Conclusion: Medial open-wedge osteotomy can adequately correct the posttraumatic varus malunion of the distal femur. With fixation of the double plate, non-displaced bone healing and good functional outcome are expected., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Background: Tibial plateau fractures are the most common intra-articular fractures, which require careful evaluation and preoperative planning. The treatment of tibial plateau fractures in elderly patients is challenging, and the comprehension of epidemiology and morphology can be helpful. This study described the characteristics of geriatric tibial plateau fractures., Methods: A total of 327 (23.24%) patients aged ≥60 years were reviewed in our level one trauma center over a 4-year period (from January 2013 to November 2016). The following parameters were collected and evaluated: (1) demographic data, (2) injury mechanisms and (3) fracture classifications., Results: Females accounted for 60.86% in all included elderly patients. Electric-bike accidents were the cause of 32.42% of all these injuries, and 39.62% of these led to high-energy injuries. The most common type of fracture was Schatzker II (54.74%). According to the three-column classification, single lateral column fracture (28.75%) and four-quadrant fracture (involving lateral, medial, posterolateral and posteromedial fractures) (23.24%) were the two most frequent patterns. In all cases, 67.58% involved the posterior column, and the prevalence of posterolateral and posteromedial fractures were 62.69% and 37.92% respectively. Isolated posterior column fractures accounted for 12.54% of patients in total, which mostly consisted of posterolateral fracture in older females (85.37%)., Conclusions: The majority of elderly patients with tibial plateau fractures are females, and Electric-bike accidents are an important cause of injury. Geriatric tibial plateau fractures have unique distribution in classification.

Previous evidence has suggested that puerarin may attenuate cardiac hypertrophy; however, the potential mechanisms have not been determined. Moreover, the use of puerarin is limited by severe adverse events, including intravascular hemolysis. This study used a rat model of abdominal aortic constriction (AAC)-induced cardiac hypertrophy to evaluate the potential mechanisms underlying the attenuating efficacy of puerarin on cardiac hypertrophy, as well as the metabolic mechanisms of puerarin involved. We confirmed that puerarin (50 mg/kg per day) significantly attenuated cardiac hypertrophy, upregulated Nrf2, and decreased Keap1 in the myocardium. Moreover, puerarin significantly promoted Nrf2 nuclear accumulation in parallel with the upregulated downstream proteins, including heme oxygenase 1, glutathione transferase P1, and NAD(P)H:quinone oxidoreductase 1. Similar results were obtained in neonatal rat cardiomyocytes (NRCMs) treated with angiotensin II (Ang II; 1 μ M) and puerarin (100 μ M), whereas the silencing of Nrf2 abolished the antihypertrophic effects of puerarin. The mRNA and protein levels of UGT1A1 and UGT1A9, enzymes for puerarin metabolism, were significantly increased in the liver and heart tissues of AAC rats and Ang II-treated NRCMs. Interestingly, the silencing of Nrf2 attenuated the puerarin-induced upregulation of UGT1A1 and UGT1A9. The results of chromatin immunoprecipitation-quantitative polymerase chain reaction indicated that the binding of Nrf2 to the promoter region of Ugt1a1 or Ugt1a9 was significantly enhanced in puerarin-treated cardiomyocytes. These results suggest that Nrf2 is the key regulator of antihypertrophic effects and upregulation of the metabolic enzymes UGT1A1 and UGT1A9 of puerarin. The autoregulatory circuits between puerarin and Nrf2-induced UGT1A1/1A9 are beneficial to attenuate adverse effects and maintain the pharmacologic effects of puerarin., (Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.)

Objectives: Researchers continue to seek easier ways to evaluate the quality of bone and screen for osteoporosis and osteopenia. Until recently, radiographic images of various parts of the body, except the distal femur, have been reappraised in the light of dual-energy X-ray absorptiometry (DXA) findings. The incidence of osteoporotic fractures around the knee joint in the elderly continues to increase. The aim of this study was to propose two new radiographic parameters of the distal femur for the assessment of bone quality., Methods: Anteroposterior radiographs of the knee and bone mineral density (BMD) and T-scores from DXA scans of 361 healthy patients were prospectively analyzed. The mean cortical bone thickness (CBTavg) and the distal femoral cortex index (DFCI) were the two parameters that were proposed and measured. Intra- and interobserver reliabilities were assessed. Correlations between the BMD and T-score and these parameters were investigated and their value in the diagnosis of osteoporosis and osteopenia was evaluated., Results: The DFCI, as a ratio, had higher reliability than the CBTavg. Both showed significant correlation with BMD and T-score. When compared with DFCI, CBTavg showed better correlation and was better for predicting osteoporosis and osteopenia., Conclusion: The CBTavg and DFCI are simple and reliable screening tools for the prediction of osteoporosis and osteopenia. The CBTavg is more accurate but the DFCI is easier to use in clinical practice. Cite this article : Q-F. He, H. Sun, L-Y. Shu, Y. Zhu, X-T. Xie, Y. Zhan, C-F. Luo. Radiographic predictors for bone mineral loss: Cortical thickness and index of the distal femur. Bone Joint Res 2018;7:468-475. DOI: 10.1302/2046-3758.77.BJR-2017-0332.R1., Competing Interests: Conflict of Interest Statement: No conflicts of interest

Puerarin is an isoflavone isolated from Radix puerariae . Emerging evidence shown that puerarin possesses therapeutic benefits that aid in the prevention of cardiovascular diseases. In this study, we evaluated the effects of puerarin on oxidative stress and cardiac fibrosis induced by abdominal aortic banding (AB) and angiotensin II (AngII). We also investigated the mechanisms underlying this phenomenon. The results of histopathological analysis, as well as measurements of collagen expression and cardiac fibroblast proliferation indicated that puerarin administration significantly inhibited cardiac fibrosis induced by AB and AngII. These effects of puerarin may reflect activation of Nrf2/ROS pathway. This hypothesis is supported by observed decreases of reactive oxygen species (ROS), decreases Keap 1, increases Nrf2 expression and nuclear translocation, and decreases of collagen expressions in cardiac fibroblasts treated with a combination of puerarin and AngII. Inhibition of Nrf2 with specific Nrf2 siRNA or Nrf2 inhibitor brusatol attenuated anti-fibrotic and anti-oxidant effects of puerarin. The metabolic effects of puerarin were mediated by Nrf2 through upregulation of UDP-glucuronosyltransferase (UGT) 1A1. The Nrf2 agonist tBHQ upregulated protein expression of UGT1A1 over time in cardiac fibroblasts. Treatment with Nrf2 siRNA or brusatol dramatically decreased UGT1A1 expression in puerarin-treated fibroblasts. The results of chromatin immunoprecipitation-qPCR further confirmed that puerarin significantly increased binding of Nrf2 to the promoter region of Ugt1a1 . Western blot analysis showed that puerarin significantly inhibited AngII-induced phosphorylation of p38-MAPK. A specific inhibitor of p38-MAPK, SB203580, decreased collagen expression, and ROS generation induced by AngII in cardiac fibroblast. Together, these results suggest that puerarin prevents cardiac fibrosis via activation of Nrf2 and inactivation of p38-MAPK. Nrf2 is the key regulator of anti-fibrotic effects and upregulates metabolic enzymes UGT1A1. Autoregulatory circuits between puerarin and Nrf2-regulated UGT1A1 attenuates side effects associated with treatment, but it does not weaken puerarin's pharmacological effects.

Perpose: To evaluate the clinical effect of united crowns or bridges for restoration of posterior teeth with insufficient maxillary bone by means of tilted dental implants., Methods: Patients who underwent dental implant surgery in posterior teeth with insufficient maxillary bone were collected and divided into two groups (40 in each group). Patients in the experimental group were treated with titled dental implantation, while patients in the control group were treated with maxillary sinus lifting. Implant retention, marginal bone loss, incidence of adverse reactions, time needed for implantation and cost were recorded and analyzed with SPSS 19.0 software package., Results: After follow up of 2 year, the experimental group had a cumulative survival rate of 100%, marginal bone resorption was (0.31±0.27)mm on average, no sinusitis and massive haemorrhage were noted, The control group had a cumulative survival rate of 96.43%, marginal bone resorption was (0.28±0.26) mm on average, sinusitis and massive haemorrhage occurred in 9.5%,4.8% of patients, the difference was not statistically significant（P＞0.05）. In the experimental group, maxillary sinus mucosa perforation and postoperative pain occurred in 0%,7.5% of patients, duration of operation was （30.55±8.21）min, average cost of each implant was （6.9±0.5）thousand RMB; while in the control group, maxillary sinus mucosa perforation and postoperative pain occurred in 14.3%,28.6% of patients, duration of operation was （50.32±10.80）min, average cost of each implant was (0.98±0.06) thousand RMB, the difference was significant（P＜0.05）., Conclusions: It is feasible to use united crowns or bridges for restoration of posterior teeth with insufficient maxillary bone by means of maxillary tuberosity dental implants.

Purpose: Direct location of the "safe zone" on a CT axial view is impossible because the radial head is circular in shape. Previous "safe zone" location methods are not appropriate if the physician is unable to visualize the actual radial head. This study aims to introduce a new method to locate the "safe zone" on CT., Methods: CT scans were performed on 20 intact cadaveric upper limbs from 20 different corpses in full pronation and supination. The DICOM-format raw data were then re-sliced and analyzed in Mimics 17.0 (Materialise, Belgium). The radial interosseous border (IB) is shaped like a droplet on the axial view; its axis was selected as our reference line (RL). A parallel line in the radial head axial slice was created, and its position relative to the "safe zone" was studied. Deviation in RL direction was evaluated., Results: Safe-zone scope was 114.41°±11.99. The rotation angle from the RL to the safe-zone's anterior and posterior border was 215.03°±5.99 and 100.62°±8.12, respectively. Rotation direction (clockwise or anti-clockwise) depended on relative radius-ulna position. The safe zone was located by determining these two borders. The reference line's direction was stable in the upper half of the IB; its distance to the radial head fovea was 77.33° mm±6.24., Conclusions: The radial head "safe zone" can be located on CT axial view based on the upper half of the IB using this new method. The method is clinically applicable to determine whether postoperative elbow malrotation results from plate impingement., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Naftopidil (NAF) is widely used for the treatment of benign prostatic hyperplasia and prevention of prostate cancer in elderly men. These patients receive a combination of drugs, which involves high risk for drug-drug interaction. NAF exhibits superior efficacy but must be administered at a much higher dosage than other therapeutic drugs. We previously showed that extensive glucuronidation of NAF enantiomers caused poor bioavailability. However, the metabolic pathway and mechanism of action of NAF enantiomer remain to be elucidated. The present study was performed to identify the human UDP-glucuronosyltransferases (UGTs) responsible for the glucuronidation of NAF enantiomers and to investigate the potential inhibition of UGT activity by NAF. The major metabolic sites examined were liver and kidney, which were compared with intestine. Screening of 12 recombinant UGTs showed that UGT2B7 primarily contributed to the metabolism of both enantiomers. Moreover, enzyme kinetics for R(+)-NAF, UGT2B7 (mean K m , 21 μM; mean V max , 1043 pmol/min/mg) showed significantly higher activity than observed for UGT2B4 and UGT1A9. UGT2B4 (mean K m , 55 μM; mean V max , 1976 pmol/min/mg) and UGT2B7 (mean K m , 38 μM; mean V max , 1331 pmol/min/mg) showed significantly higher catalysis of glucuronidation of S(-)-NAF than UGT1A9. In human liver microsomes, R(+)-NAF and S(-)-NAF also inhibited UGT1A9: mean K i values for R(+)-NAF and S(-)-NAF were 10.0 μM and 11.5 μM, respectively. These data indicate that UGT2B7 was the principal enzyme mediating glucuronidation of R(+)-NAF and S(-)-NAF. UGT2B4 plays the key role in the stereoselective metabolism of NAF enantiomers. R(+)-NAF and S(-)-NAF may inhibit UGT1A9. Understanding the metabolism of NAF enantiomers, especially their interactions with metabolic enzymes, will help to elucidate potential drug-drug interactions and to optimize the administration of this medicine.

Background: A coronal fracture of the posterior femoral condyle, also known as a Hoffa fracture, is an unusual injury, and there are only a handful of case reports or series exploring it. The optimal fixation method of these intraarticular fractures remains controversial; improper or unstable fixation usually lead to an unsatisfactory prognosis. The use of posterior-anterior or reversed lag screw fixation is still a popular method. Additional buttress plating is also recommended for fixation of these difficult fractures. The purpose of this study was to compare the mechanical strength of four different fixation patterns for this uncommon fracture., Material and Methods: Sixteen sawbone simulated models of Letenneur type I Hoffa fractures were created with one of four fixation patterns: two screws implanted in the anterior-posterior (AP) direction or posterior-anterior (PA) direction; one screw in the PA direction with a plate implanted in the posterior position of the distal femoral condyle or with a plate in the lateral position. Biomechanical testing was performed to determine the post-fixation axial stiffness, the maximum load to failure and the fragment vertical displacement for each of the four constructs., Results: The plate fixation patterns whether implanted in the posterior or lateral position were shown to provide higher overall axial stiffness and load to failure, and less vertical displacement than the other two patterns of pure screw fixation. Among these constructs, the lateral plate fixation was found to provide the highest stiffness and load to failure and the least displacement for the posterior condylar fragments, followed by the posterior plate fixation. The lowest overall stiffness and load to failure and the largest vertical displacement were found in the construct with the AP direction placed screws., Conclusion: It was concluded that the lateral position implanted plate is biomechanically the strongest fixation method for Letenneur type I Hoffa fractures. However, this plate fixation is not recommended for all cases. The choice of internal fixation pattern depends on the surgeons., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This study aimed to investigate the anti-oxidant and anti-hypertrophic effects of puerarin-7-O-glucuronide, a water-soluble puerarin metabolite. The anti-oxidant effects of puerarin-7-O-glucuronide were assessed by measurement of intracellular superoxide levels, total superoxide dismutase (SOD) activity, total anti-oxidant capacity, and glutathione (GSH)/glutathione disulfide (GSSG) ratio in cultured neonatal rat cardiomyocytes (NRCMs) stimulated with the xanthine oxidase (XO)/xanthine (X) system or angiotensin II. The activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and expression of NADPH oxidase subunits p22 phox and p47 phox were determined. The anti-hypertrophic effects of puerarin-7-O-glucuronide in angiotensin II-challenged NRCMs were characterized by changes in cell morphology and expression of hypertrophic genes. In the pharmacokinetic study, the plasma concentration of puerarin-7-O-glucuronide was determined by rapid resolution-liquid chromatography-tandem mass spectrometry (RR-LC-MS/MS). Puerarin-7-O-glucuronide prevented XO/X-induced increase in intracellular superoxide production and decreases in total SOD activity, GSH/GSSG ratio, and total anti-oxidant capacity. Puerarin-7-O-glucuronide also reversed angiotensin II-induced increases in intracellular superoxide production and NADPH oxidase activity and decreases in total SOD activity. These anti-oxidant effects of puerarin-7-O-glucuronide were accompanied by downregulation of p22 phox and p47 phox . Furthermore, puerarin-7-O-glucuronide prevented angiotensin II-induced increases in cell surface area and perimeter, as well as changes in Nppa, Myh7, and Myh6. In the pharmacokinetic study, puerarin-7-O-glucuronide was cleared with a half-life of 0.94 h after intravenous administration. Puerarin could be detected in rat plasma, albeit in low concentration, as early as 5 min after intravenous administration of puerarin-7-O-glucuronide. These anti-oxidant and anti-hypertrophic properties of puerarin-7-O-glucuronide were similar to those of its parent compound puerarin. These results support the development of puerarin-7-O-glucuronide as a novel pharmaceutical agent for therapeutic application.

Background: This study aimed to explore the cellular morphology of respiratory epithelium in Mycoplasma pneumonia (MpP) patients., Materials and Methods: The cast-off cell morphological findings from bronchoscopic brushings in MpP and community-acquired pneumonia (CAP) caused by typical pathogens were reviewed., Results: Compared with the CAP group, cellular dysplasia in respiratory tract epithelial brushings was significantly greater in MpP patients ( P = 0.033)., Conclusion: Unique biological characteristics and mechanisms of pathogenesis of Mycoplasma pneumoniae (Mp) may result in dyskaryotic changes in respiratory epithelium in adult MpP., Competing Interests: There are no conflicts of interest.

Purpose: We introduce a new MIPPO procedure which is simple and effective for the treatment of extra-articular distal tibia facture (AO-43A). The aim of this retrospective study was to compare our modified MIPPO with IMN., Materials and Methods: This retrospective study included 64 patients treated with our modified MIPPO and 61 patients with IMN. The data of sex, age, operation time, blood loss, wound complications, mal-reduction, shortening and fracture healing was analyzed., Results: The operation time was significantly shorter in the MIPPO group than in the IMN group (56.0min vs. 85.0min, P<0.001). There were 5 patients (8.2%) in the IMN group and 2 patients (3.1%) in the MIPPO group who had wound complications (P=0.399). Mal-reduction occurred in 17 patients (27.9%) managed with IMN and in 3 patients (4.7%) who had MIPPO (P<0.001). Furthermore, no patients had a left/right difference in the length of the tibia of >1cm and nonunion in both groups., Conclusions: Our results have shown that our modified MIPPO has enormous advantages over IMN for extra-articular distal tibia fracture (AO-43A)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Posterior pilon variant fracture is a recently described posterior malleolus fracture characterized by the involvement of both posterolateral and posteromedial malleolar fragment. The associated surgical approach remains controversial. The aim of this study was to present the application of modified posteromedial approach in the treatment for posterior pilon variant fracture., Methods: Sixteen patients were identified with posterior pilon variant fractures. All fractures were operated via modified posteromedial approach. Fragment length ratio, area ratio and height were measured as morphologic assessments. The clinical outcome was evaluated with American Orthopaedic Foot & Ankle Society ankle-hind foot score and visual analogue scale. Radiological images were evaluated using osteoarthritis-score., Results: According to the radiological measurements, the average fragment length ratio of posteromedial and posterolateral fragment was 25.3 and 31.5 % respectively. All fractures healed within a mean period of 13.1 weeks without malalignment or articular step-off. Fourteen patients were followed up, and all achieved good or excellent ankle function. The average score of American Orthopaedic Foot & Ankle Society and visual analogue scale at rest, motion and weight bearing walking was 85.6 and 0.25, 0.81, 1.31 respectively., Conclusion: Modified posteromedial approach provides an alternative surgical treatment for posterior pilon variant fractures, and the short-term outcome was good.

Objective: Atrial fibrillation (AF) is responsible for some thromboembolic events. Asymmetrical dimethylarginine(ADMA) increases in atrial fibrillation(AF) animals with dysfunction of endothelium, but its role in pro-thrombotic state of AF was unknown. The aim of our study was to explore the role of ADMA in predicting the pro-thrombotic state in AF and to reveal its mechanism., Methods: One hundred and thirty-eight patients in the First Affiliated Hospital, Sun Yat-sen University, from 2010 to 2012, were enrolled (persistent atrial fibrillation group, PAF, n=80; paroxysmal atrial fibrillation group, Paf, n=30; sinus rhythm, SR, n=28). Plasma ADMA levels were detected by ELISA-kits. CHADS2 and CHA2DS2-VASc scores were estimated for each patient.14 Beagles (pacing group, n=8; sham group, n=6) were subjected to rapid atrial pacing (RAP). ADMA level was detected after 4 weeks of RAP., Results: ADMA level was elevated significantly in patients with atrial fibrillation especially in patients with persistent atrial fibrillation, and showed a significant linear correlation to CHADS2 and CHA2DS2-VASc score. With ADMA, ROC area under the curve was 0.865 in CHADS2 score ≥2 and was 0.959 in CHA2DS2-VASc score ≥2 (P<0.001 respectively). After 4 weeks of RAP, ADMA level was elevated compared to sham group and before operation. ADMA showed a linear correlation with atrial fibrillation susceptibility(r=0.686, P=0.007)., Conclusions: ADMA levels are elevated both in AF patients and RAP beagles. ADMA correlates with stroke risk concerning with CHADS2/CHA2DS2-VASc score. ADMA may become a new biomarker for predicting pro-thrombotic risk in AF.

Background: The incidence of pelvic fractures in trauma patients is reported to be 3-8.2%, with roughly half of these fractures being caused by high energy injuries with a potential for catastrophic hemorrhage and death. Indications for internal fixation of anterior pelvic ring are controversial. Because of fears of disturbing the pelvic hematoma and causing additional hemorrhage, open reduction and internal fixation of pelvic ring disruption is routinely delayed. In contrast to conventional surgery, percutaneous screw fixation is gaining popularity in the treatment of pelvic and acetabular fractures mainly because of minimal soft tissue damage, less operative blood loss, early surgical intervention and comfortable mobilization of the patient. Fluoro-navigation is a new surgical technique in orthopedic trauma surgery. This study is to investigate clinical results of fluoro-navigation surgery in anterior pelvic ring fractures., Materials and Methods: From January 2006 to October 2011, 23 patients with anterior pelvic ring fractures were treated with percutaneous cannulated screw under fluoro-navigation. There were 14 men and 9 women, with a mean age of 40.1 years (range 25-55). According to the AO and Orthopedic Trauma Association classification, there were seven A 2.1, two A 2.2, one A 2.3, six B 1.2, one B 2.1: 1, one B 2.2, one C 1.2, two C 1.3 and two C 2.3 types of fractures. Amongst these patients, 13 had posterior pelvic ring injuries, 8 had other injuries including urethral, lumbar vertebrae fractures and femoral fractures. All patients were operated when their general condition stabilized after emergency management. The mean time from injury to percutaneous screw fixation of the anterior pelvic ring fracture was 12 days (3-15 days). All the anterior ring fractures were fixed with cannulated screws by two senior surgeons. They were familiar with the navigation system and had gained much experience in the computer-assisted percutaneous placement of screws., Results: A total of 32 screws were inserted, including 19 in the pubic ramis and 13 in the anterior acetabular columns. The average surgical time was 23.3 min/screw. The average time of X-ray exposure was 19.1 ± 2.5 s/screw. The virtual images of fluoro-navigation were compared with real-time X-rays during and after the surgery. Compared to the final position of the screw, the average deviated distance was 3.11 mm and the average trajectory difference was 2.81°. Blood loss during the operation was minimal (22.3 ml/screw). One screw (3.1%) deviated out of the fracture site during the operation. No superficial or deep infection occurred. No patient sustained recognized neurologic, vascular, or urologic injury as a result of the percutaneous screw fixation. All fractures united at the last followup., Conclusions: Fluoro-navigation technique could become a safe, accurate, and fairly quick method for the treatment of anterior pelvic ring fractures. Standardization of the operative procedure and training are mandatory for the success of this procedure.

The endothelial-mesenchymal transition (EndMT) is known to play a central role in the pathological process of heterotopic ossification (HO). Based on the ability of SMAD7 (mothers against decapentaplegic homolog 7) to block EndMT-related processes such as myofibroblast transformation, we hypothesized that SMAD7 may be a potential therapeutic target for HO. We constructed a lentivirus overexpressing SMAD7 and tested on rat aortic endothelial cells for optimal titre and transduction efficiency. The lentivirus was then injected into a surgical rat model of Achilles tendon injury. Expression of endothelial markers and mesenchymal markers at the injury sites was subsequently quantified by qPCR and western analysis. Lentiviral delivery of SMAD7 in vivo resulted in an upregulation of endothelial markers (CD31, VE-cadherin) and a downregulation of mesenchymal markers (N-cadherin and vimentin), suggesting that EndMT is blocked due to local SMAD7 overexpression. The difference is more apparent at 10 weeks than at 6 weeks after surgery. X-ray imaging and histological staining further confirmed the absence of ossified structure in the tendon tissue injected with SMAD7-delivering lentivirus, as opposed to the control groups. Post-surgical HO may be prevented in vivo by local delivery of SMAD7 without affecting the normal wound-healing process. These data advance our understanding of the HO process at the molecular level, and provide additional avenues for the prevention and treatment of postoperative HO., (© 2016 Federation of European Biochemical Societies.)

Background: There are few posterolateral approaches that do not require the common peroneal nerve (CPN) dissection. With the nerve exposure, it would pose a great challenge and sometimes iatrogenic damage over the surgical course. The purpose was to present a case series of patients with posterolateral tibial plateau fractures treated by direct exposure and plate fixation through a modified posterolateral approach without exposing the common peroneal nerve (CPN)., Materials and Methods: 9 consecutive cases of isolated posterior fractures of the posterolateral tibial plateau were operated by open reduction and plate fixation through the modified posterolateral approach without exposing the CPN between June 2009 and January 2012. Articular reduction quality was assessment according to the immediate postoperative radiographs. At 24 month followup, all patients had radiographs and were asked to complete a validated outcome measure and the modified Hospital for Special Surgery (HSS) Knee Scale., Results: All patients were followedup, with a mean period of 29 months (range 25-40 months). Bony union was achieved in all patients. In six cases, the reduction was graded as best and in three cases the reduction was graded as middle according to the immediate postoperative radiographs by the rank order system. The average range of motion arc was 127° (range 110°-134°) and the mean postoperative HSS was 93 (range 85-97) at 24 months followup. None of the patients sustained neurovascular complication., Conclusions: The modified posterolateral approach through a long skin incision without exposing the CPN could help to expand the surgical options for an optimal treatment of this kind of fracture, and plating of posterolateral tibial plateau fractures would result in restoration and maintenance of alignment. This approach demands precise knowledge of the anatomic structures of this region.

Background. The optimal timing for Bone Marrow Stem Cells (BMCs) therapy following acute myocardial infarction (AMI) remains unclear. Aims. To synthesize the evidence from trials using a multiple-treatment comparison method, thereby permitting a broader comparison across multiple timing of BMCs therapy. Methods and Results. Randomized controlled trials in patients with AMI receiving BMCs therapy were identified from PubMed, Ovid LWW, BIOSIS Previews, and the Cochrane Library through January 2015. 2 035 patients of 31 studies included in our analysis were allocated to 5 groups' treatments: 1~3 days, 4~7 days, 8~14 days, 15~30 days, or placebo/control group. The multiple-treatment meta-analysis showed that 4~7 days' group could lead to significantly increased left ventricular ejection fraction (LVEF) as compared with control (mean of MDs and 95% CI: 6 months, 3.05 (0.92~5.25); 12 months, 4.18 (2.30~5.84)). Only 4~7 days led to significant reduction of MACEs compared with control (OR and 95% CI 0.34 (0.13~0.96)) for 12-months follow-up. In simulated comparisons, the 4~7 days' group ranked better than other timing groups for improvement of LVEF or reduction of the incidence of major adverse cardiac events. Conclusions. 4~7 days after AMI might be the optimal timing for cell therapy in terms of efficacy or safety.

Objective: Open reduction and internal fixation of two column posterior and lateral tibial plateau fractures through a combined posterior reversed L-shaped and anterolateral approach in floating position in Caucasians., Indications: Two column posterior and lateral tibial plateau fractures., Contraindications: Tibial plateau fractures that do not involve the posterior and lateral column., Surgical Technique: The patient is positioned in floating position, a reversed L-shaped skin incision is made, the posterior column after lateral retraction of the medial head of the gastrocnemius muscle is exposed, and the posterior fragments are reduced and fixed. Subsequently, flexion and varus stress on the knee is applied, an anterolateral skin incision is made, the lateral column is exposed, and the lateral fragments are reduced and fixed., Conclusion: Despite a different physique as Asians, a combined posterior reversed L-shaped and anterolateral approach in a floating position for the surgical treatment of two column posterior and lateral tibial plateau fractures is technically possible in Caucasians. In our experience, this combined approach is an excellent strategy in most patients for surgical treatment of two column posterior and lateral column fractures., (Copyright © 2015 Elsevier Ltd. All rights reserved.)