Background: With the recent rise in anterior cruciate ligament (ACL) reconstruction surgeries in China, a corresponding increase in surgical failures has been observed. Variability in primary surgical techniques and the intricacies of failure mechanisms have introduced significant challenges in diagnosing failures, planning procedures, and conducting revision surgeries. Methods: In response to these challenges, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) initiated the development of an expert consensus on ACL reconstruction failure and revision. Utilizing a modified Delphi method, 67 domestic experts from relevant fields were invited for consensus formulation and review. Results: The expert panel achieved a high degree of consensus on twelve key aspects. The consensus clearly defines ACL reconstruction failure and outlines multiple contributing factors, with surgical errors, especially incorrect bone tunnel placement, identified as primary causes. It also emphasizes the significant impact of patient-specific variables on the likelihood of failure. Recommendations for revision surgeries include careful determination of revision indications, preserving meniscal integrity to reduce the risk of joint degeneration, and a preference for single-stage or two-stage surgeries based on individual patient evaluations. A unified approach for managing bone defects remains absent, necessitating comprehensive assessments. Graft selection should be tailored to each patient, with autografts, allografts, or synthetic ligaments as viable options. For patients with a highly positive pivot shift test or those engaged in high-demand athletic activities, anterolateral structure augmentation or reconstruction is recommended. Conclusion: The consensus emphasizes the critical need for individualized approaches in ACL revision surgery. By clearly defining failure criteria and outlining strategies for surgical revisions, these statements are expected to serve as a guide for refining clinical practice, reducing complications, and improving surgical outcomes. The translational potential of this article: 1) Establishment of Evidence-Based Clinical Guidelines: This article presents a rigorously developed expert consensus on ACL reconstruction failure and revision, providing evidence-based clinical guidelines that are directly applicable in surgical practice. The standardization of these protocols across medical institutions has the potential to reduce variability in patient care and improve surgical outcomes on a national scale. 2) Advancement of Precision Medicine in ACL Surgery: By emphasizing the need for patient-specific approaches in the management of ACL reconstruction failure, this consensus supports the advancement of precision medicine in orthopaedic surgery. The tailored recommendations for graft selection, surgical techniques, and rehabilitation protocols can lead to more personalized and effective treatments, reducing the risk of complications and enhancing recovery. 3) Catalyst for Innovation in Surgical Techniques: The article identifies critical gaps and challenges in current ACL revision practices, providing a foundation for future research and innovation. By outlining the complexities and controversies in surgical decision-making, this work serves as a catalyst for the development of new surgical techniques and technologies aimed at improving patient outcomes. 4) Framework for Future Research and Development: The consensus not only addresses immediate clinical needs but also sets a clear agenda for future research in ACL revision. By offering a structured approach to the diagnosis and management of ACL failures, this article guides both basic and translational research efforts, ensuring that future innovations are aligned with clinical realities and patient needs.
The effects of the menstrual cycle and sex hormones on knee kinematics remain unclear. The purpose of the study was to investigate the effects of the menstrual cycle and serum sex hormone concentrations on knee kinematic parameters of the 90°cutting in female college soccer athletes. Three female college soccer teams (53 subjects) participated in the study. During the first menstrual cycle, a three-step method was used to exclude subjects with anovulatory and luteal phase–deficient (LPD) (12 subjects). The subjects’ menstrual cycle was divided into the menstrual phase, late-follicular phase, ovulatory phase, and mid-luteal phase (group 1, 2, 3, 4). In each phase of the second menstrual cycle, we used a portable motion analysis system to enter the teams and tested the sex hormones concentrations and knee kinematics parameters in three universities in turn. We found that subjects had a lower maximum knee valgus in group 4 compared with other groups. This meant that subjects had a lower biomechanical risk of non-contact anterior cruciate ligament (ACL) injury in the mid-luteal phase. There was no significant correlation between serum estrogen, progesterone concentration, and knee kinematic parameters. This meant that sex hormones did not have a protective effect. Future studies need to incorporate more factors (such as neuromuscular control, etc.) to investigate.
Background:With the increasing physical activity level in elderly population, anterior cruciate ligament (ACL) injuries are becoming more frequent. Due to the possible surgery complications, treatment for ACL rupture in patients with advanced age is still controversial. The purpose of this study was to compare the therapeutic effects of reconstruction using the ligament advanced reinforcement system (LARS) artificial ligament in patients older than 50 and patients younger than 50 with chronic ACL rupture. Methods:Indications included: (I) concurrent history of subjective symptomatic anterior knee instability despite nonoperative rehabilitation for least 3 months, (II) positive preoperative Lachman and pivot shift tests, (III) ACL stump still connecting the femur with the tibia as demonstrated by Magnetic Resonance Imaging (MRI), and (IV) some residual ligament fibers still connecting the femur with the tibia as demonstrated by arthroscopy. Participants were divided into groups based on their age. Participants were divided into groups based on their age. A total of 37 patients who underwent reconstruction of chronic ACL rupture using the LARS artificial ligament were divided into group A (≥50 years, n=16) and group B (<50 years, n=21). Results:The outcome measures were compared between the 2 groups. These included the baseline clinical data, the International Knee Documentation Committee (IKDC) scoring system, Pivot shift test, Lachman test, Kneelax arthrometer measurements, Tegner activity scale, Lysholm knee scoring scale, and Kellgren-Lawrence radiographic classification of arthritis and complications. Postoperative knee laxity and the functional examination were significantly improved compared to preoperative measurements for both groups (all P<0.01). No significant differences were found in postoperative knee laxity and functional examination between the 2 groups (all P>0.05). The level of osteoarthritis did not statistically increase in either group during follow-up (all P>0.05). No complications associated with the arthroscopic surgery were found in either group. Conclusions:The reconstruction of chronic ACL rupture using the LARS artificial ligament showed similar therapeutic effects in patients over the age of 50 and those under the age of 50.
Long noncoding RNAs (lncRNAs), as a novel regulatory factor, are considered to play a vital role in various biological processes and diseases.However, the overall expression profile and biological functions of lncRNAs in the partially injured anterior cruciate ligament(ACL) and medial collateral ligament(MCL) have not been clearly explored.Partially injured models of ACL and MCL were established in 3-month-old healthy male New Zealand white rabbits.Expression of lncRNAs and mRNAs in the ligament tissue was detected by highthroughput sequencing technology, and biological functions of differentially expressed RNAs were evaluated by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis.Validation of several differentially expressed RNAs was performed using quantitative real-time PCR(qRT-PCR).Protein-protein interaction (PPI) analysis and competitive endogenous RNA (ceRNA) prediction were used to identify interactions among hub genes and the interaction among lncRNAs, miRNAs, and mRNAs.The results showed that compared with the normal group, there were 267 mRNAs and 329 lncRNAs differentially expressed in ACL and 726 mRNAs and 609 lncRNAs in MCL in the injured group.Compared with MCL, 420 mRNAs and 470 lncRNAs were differentially expressed in ACL in the normal group; 162 mRNAs and 205 lncRNAs were differentially expressed in ACL in the injured group.Several important lncRNAs and genes were identified, namely, COL7A1, LIF, FGFR2, EPHA2, CSF1, MMP2, MMP9, SOX5, LOX, MSTRG.1737.1,MSTRG.26038.25,MSTRG.20209.5,MSTRG.22764.1, and MSTRG.18113.1, which are closely related to inflammatory response, tissue damage repair, cell proliferation, differentiation, migration, and apoptosis.Further study of the functions of these genes may help to better understand the specific molecular mechanisms underlying the occurrence of endogenous repair disorders in ACL, which may provide new ideas for further exploration of effective means to promote endogenous repair of ACL injury.
Long noncoding RNAs (lncRNAs), as a novel regulatory factor, are considered to play a vital role in various biological processes and diseases.However, the overall expression profile and biological functions of lncRNAs in the partially injured anterior cruciate ligament(ACL) and medial collateral ligament(MCL) have not been clearly explored.Partially injured models of ACL and MCL were established in 3-month-old healthy male New Zealand white rabbits.Expression of lncRNAs and mRNAs in the ligament tissue was detected by highthroughput sequencing technology, and biological functions of differentially expressed RNAs were evaluated by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis.Validation of several differentially expressed RNAs was performed using quantitative real-time PCR(qRT-PCR).Protein-protein interaction (PPI) analysis and competitive endogenous RNA (ceRNA) prediction were used to identify interactions among hub genes and the interaction among lncRNAs, miRNAs, and mRNAs.The results showed that compared with the normal group, there were 267 mRNAs and 329 lncRNAs differentially expressed in ACL and 726 mRNAs and 609 lncRNAs in MCL in the injured group.Compared with MCL, 420 mRNAs and 470 lncRNAs were differentially expressed in ACL in the normal group; 162 mRNAs and 205 lncRNAs were differentially expressed in ACL in the injured group.Several important lncRNAs and genes were identified, namely, COL7A1, LIF, FGFR2, EPHA2, CSF1, MMP2, MMP9, SOX5, LOX, MSTRG.1737.1,MSTRG.26038.25,MSTRG.20209.5,MSTRG.22764.1, and MSTRG.18113.1, which are closely related to inflammatory response, tissue damage repair, cell proliferation, differentiation, migration, and apoptosis.Further study of the functions of these genes may help to better understand the specific molecular mechanisms underlying the occurrence of endogenous repair disorders in ACL, which may provide new ideas for further exploration of effective means to promote endogenous repair of ACL injury.
Objective This study was designed to evaluate the operability, effectiveness, and safety of the automated titanium suture fastener in a preclinical ovine model in comparison with manual tying in a mitral valve annuloplasty ring implantation surgery. Methods Eighteen adult Small-tailed Han sheep were prepared for the surgery of mitral valve annuloplasty ring implantation through lateral thoracotomy under cardiopulmonary bypass (CBP). A total of 12 stitches were performed to secure an annuloplasty ring, with 6 stitches done with the automated fastener and the other 6 by manual tying. The knotting time for the automated fastener or manual tying was recorded, respectively. The firmness of knots, mitral valve integrity, biocompatibility, thrombosis, local reactions, and other aspects were also compared at follow-up time (Days 30, 60, 90, and 180). Results Of the 18 sheep, 16 survived to the designated endpoints and were enrolled for further analysis. Compared with the control group, the knotting time was significantly reduced with the automated fastener (p < 0.01). All the annuloplasty rings were tightly secured by 6 fastener clips and 6 hand-made knots without any disengagement or displacement. All the mitral valves were intact without any defect, stenosis, prolapse, valve insufficiency, or perforation. Endothelialization was comparable between the two groups by Day 60. Small red thrombi formed at the thread end of the suture in both groups. No thrombus was found on the surface of the titanium clip. All the thrombi were within the acceptable range for the antithrombotic property. Thrombosis showed no significant difference by Day 60. No significant differences in the inflammatory response and pathological lesions were observed by Day 60. One case of diffuse renal infarction (area ratio = 20%) and 1 case of small focal renal infarction (area ratio < 5%) were caused by thromboembolism. Conclusions The automated fastener significantly shortened the procedure time of tying knots for the implantation of the annuloplasty ring in the ovine model, with comparable safety and effectiveness as manual tying.
Long noncoding RNAs (lncRNAs), as a novel regulatory factor, are considered to play a vital role in various biological processes and diseases. However, the overall expression profile and biological functions of lncRNAs in the partially injured anterior cruciate ligament (ACL) and medial collateral ligament (MCL) have not been clearly explored. Partially injured models of ACL and MCL were established in 3-month-old healthy male New Zealand white rabbits. Expression of lncRNAs and mRNAs in the ligament tissue was detected by high-throughput sequencing technology, and biological functions of differentially expressed RNAs were evaluated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Validation of several differentially expressed RNAs was performed using quantitative real-time PCR (qRT-PCR). Protein-protein interaction (PPI) analysis and competitive endogenous RNA (ceRNA) prediction were used to identify interactions among hub genes and the interaction among lncRNAs, miRNAs, and mRNAs. The results showed that compared with the normal group, there were 267 mRNAs and 329 lncRNAs differentially expressed in ACL and 726 mRNAs and 609 lncRNAs in MCL in the injured group. Compared with MCL, 420 mRNAs and 470 lncRNAs were differentially expressed in ACL in the normal group; 162 mRNAs and 205 lncRNAs were differentially expressed in ACL in the injured group. Several important lncRNAs and genes were identified, namely, COL7A1, LIF, FGFR2, EPHA2, CSF1, MMP2, MMP9, SOX5, LOX, MSTRG.1737.1, MSTRG.26038.25, MSTRG.20209.5, MSTRG.22764.1, and MSTRG.18113.1, which are closely related to inflammatory response, tissue damage repair, cell proliferation, differentiation, migration, and apoptosis. Further study of the functions of these genes may help to better understand the specific molecular mechanisms underlying the occurrence of endogenous repair disorders in ACL, which may provide new ideas for further exploration of effective means to promote endogenous repair of ACL injury.
With the increase of the aging population, the high mortality and disability rates caused by ischemic stroke are some of the major problems facing the world, and they dramatically burden the society. Panax notoginseng (Burk) F. H. Chen, a traditional Chinese medicine, is commonly used for promoting blood circulation and removing blood stasis, and its main bioactive components are Panax notoginseng saponins (PNS). Therefore, we performed a meta-analysis on focal cerebral ischemia-reperfusion animal models established with middle cerebral artery occlusion (MCAO) surgery to evaluate the therapeutic effect of PNS. We systematically searched the reports of PNS in MCAO animal experiments in seven databases. We assessed the study quality using two literature quality evaluation criteria; evaluated the efficacy of PNS treatment based on the outcomes of the neurological deficit score (NDS), cerebral infarct volume (CIV), and biochemical indicators via a random/fixed-effects model; and performed a subgroup analysis utilizing ischemia duration, drug dosage, intervention time, and administration duration. We also compared the efficacy of PNS with positive control drugs or combination treatment. As a result, we selected 14 eligible studies from the 3,581 searched publications based on the predefined exclusion-inclusion criteria. PNS were significantly associated with reduced NDS, reduced CIV, and inhibited release of the inflammatory factors IL-1 beta and TNF-alpha in the focal MCAO rat models. The PNS combination therapy outperformed the PNS alone. In addition, ischemia time, drug dosage, intervention time, and administration duration in the rat models all had significant effects on the efficacy of PNS. Although more high-quality studies are needed to further determine the clinical efficacy and guiding parameters of PNS, our results also confirmed that PNS significantly relieves the focal cerebral ischemia-reperfusion in rat models. In the animal trials, it was suggested that an early intervention had significant efficacy with PNS alone or PNS combination treatment at a dosage lower than 25 mg/kg or 100-150 mg/kg for 4 days or longer. These findings further guide the therapeutic strategy for clinical cerebral ischemic stroke.
Objective: This study aimed to assay expression of the mRNA and proteins for injuring- and angiogenesis-associated molecules at 3 days, 1week, 2weeks, 4weeks and 6 weeks after anterior cruciate ligament or medial collateral ligament injury in male New Zealand White rabbits. Methods: Models similar to those of clinical patients were used to establish acute partial injuries of the anterior cruciate ligament and medial collateral ligament at 3 days, 1 week, 2 weeks, 4 weeks and 6 weeks and normal control groups. Molecular biological changes in male rabbits were detected at different time points after anterior cruciate ligament and medial collateral ligament injury by H&E staining, reverse transcriptase chain reaction and westren blotting. Results: Marked differences were found in the postinjury changes in gene levels and proteins in the anterior cruciate ligament compared to the medial collateral ligament. There was no increase in mRNA expression of TIMP3, TGF-βand PRG4 in the injured anterior cruciate ligament at any time point. However, the levels of these genes tended to increase in the injured medial collateral ligament. In contrast, MMP-13 mRNA levels were significantly increased in the injured anterior cruciate ligament, but not in the medial collateral ligament. Furthermore, vascular endothelial growth factor decreased following injury to both the anterior cruciate ligament and medial collateral ligament, with the difference being a slight decrease in the medial collateral ligament and a significant decrease in the anterior cruciate ligament. Similarly, protein blots showed higher protein expression of type I and type III collagen in the injured medial collateral ligament than in the anterior cruciate ligament. Conclusion: The results show that there were drastic differences in angiogenesis, collagen and Matrix metalloproteinases after anterior cruciate ligament and medial collateral ligament injury. It can be found that the repair ability of the anterior cruciate ligament and medial collateral ligament after injury may be related to the differences in molecular expression.
Background: Cardiopulmonary bypass is the basis of open heart surgery. Through simulation-based learning, residents may receive structured training of cardiopulmonary bypass techniques. Therefore, we built a high-fidelity, tissue-based simulation model for cardiopulmonary bypass cannulation/decannulation training. Methods: The core of the model is a whole block of cadaveric animal heart and lung. The discarded membrane oxygenators are used as blood reservoirs. The tubing and suckers recycled from animal experiments are washed and reused. To set up the model, the cadaveric heart and lung are placed into a container of appropriate size. The “arterial” tubing is connected with a pressure gauge, the distal aorta, the superior vena cava, and arterial cannula, respectively. The “venous” tubing is composed of three independent catheters, respectively, for the practice of venous cannulation, for the connection of sucker and for the practice of placing left atrial/ventricular vent. All tubes are installed on the roller pumps to maintain the correct flow direction. A technician should be responsible for operating the heart–lung machine, clamping and releasing the specific segments of tubing, adjusting the pressure, and cooperating with the trainees to practice. Results: Using the simulation model, 18 residents underwent cardiopulmonary bypass techniques training, with an average satisfaction of 8.94 points. The mean score on the overall fidelity of the simulation model assessed by nine experienced cardiothoracic surgeons was 8.67 points. Conclusion: The tissue-based simulation model has a certain degree of realism. Cardiac surgery residents can practice necessary cardiopulmonary bypass cannulation/decannulation techniques by this model.
目的 探讨蛋白激酶A(PKA)/钙调蛋白Ⅱ(CaMKⅡ)信号通路在二甲双胍(Met)调节2型糖尿病(T2DM)大鼠心房小电导钙激活钾通道亚型KCa2.2和KCa2.3蛋白表达中的作用.方法 健康雄性Wistar大鼠40只,随机选8只喂普通饲料为对照组(Con组),另32只喂高脂高糖饲料联合腹腔注射小剂量链脲佐菌素构建T2DM大鼠模型后,再随机分为DM组、Met组、H-89组(腹腔注射PKA抑制剂H-89)和KN-93组(腹腔注射CaMKⅡ抑制剂KN-93),每组8只.用ELISA检测大鼠心房组织PKA活性,qRT-PCR检测CaMKⅡ mRNA表达,Western blot和免疫组织化学检测KCa2.2、KCa2.3和磷酸化CaMKⅡ(p-CaMKⅡ)蛋白表达.结果 Con组、DM组、Met组和H-89组PKA活性分别为0.74±0.04、0.50±0.05、0.69±0.03和0.48±0.03.与DM组比较,Met组PKA活性明显提升(P<0.01);与Met组比较,H-89组显著抑制PKA活性(P<0.01).Con组、DM组及Met组CaMKⅡ mRNA分别为1.00±0.07、0.61±0.03和0.92±0.09.与Con组比较,DM组CaMKⅡ mRNA表达明显降低(P<0.01);与DM组比较,Met组CaMKⅡmRNA表达明显增加(P<0.01).与Con组比较,DM组心房组织p-CaMKⅡ和KCa2.2蛋白表达均明显降低,KCa2.3蛋白表达明显升高(P<0.01).与DM组比较,Met组明显提升p-CaMKⅡ和KCa2.2蛋白表达,明显抑制KCa2.3蛋白表达(P<0.01).与Met组比较,KN-93组和H-89组分别显著抑制p-CaMKⅡ蛋白表达和PKA活性,均显著下调KCa2.2蛋白表达,上调KCa2.3蛋白表达(P<0.01).免疫组织化学染色显示,与Met组比较,KN-93组和H-89组均显著下调KCa2.2蛋白表达,上调KCa2.3蛋白表达(P<0.05,P<0.01),与Western blot检测结果一致.结论 Met通过激活PKA/CaMKⅡ信号通路部分修复T2DM大鼠心房KCa2.2蛋白下调和KCa2.3蛋白上调.
Here we investigated the morphology, quantity, distribution and gene expression of mechanoreceptors in the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL), lateral collateral ligament (LCL), patellar tendon (PaT) and popliteal tendon (PoT) of the knee joint. Twelve 6-month-old rabbits were divided into two groups. In one group, the ACL, PCL, MCL, LCL, PaT and PoT were collected to observe the morphology, distribution and quantity of mechanoreceptors. In another group, the ACL, PCL, MCL, LCL, PaT and PoT of bilateral knee joints were used to determine S100B, CGRP and NEFM gene levels. Five types of mechanoreceptors were observed including Ruffini corpuscles, Pacinian corpuscles, Golgi-tendon bodies, atypical mechanoreceptors and free nerve endings. The total amount of mechanoreceptors was significantly lower in MCL, LCL, PaT and PoT as compared with ACL and PCL (P < 0.001). All examined mechanoreceptors were present in ACL, PCL and LCL. However, no Pacinian corpuscles and Golgi-tendon bodies were found in MCL and PoT as well as Pacinian corpuscles were not observed in PaT. The present study indicated that the levels of NEFM was significantly lower in PCL, MCL, LCL, PaT and PoT as compared with ACL (P < 0.05), but there was no significant difference in CGRP level between ACL and other ligaments except LCL (P > 0.05). Thus, the quantity, type and gene expression of mechanoreceptors are different in various ligaments. Thus, the quantity and distribution of mechanoreceptors may be related to ligament's function.
Objective: Many countries are facing a shortage of cardiac surgeons, who are crucial in meeting the demands of growing number of patients in need of coronary artery bypass grafting. This situation poses a serious challenge, especially in China. The purpose of this study is to determine whether cardiac surgeons are suitable for training in coronary artery anastomosis at an earlier stage in their career. Methods: We divided 12 cardiac surgeons with no prior experience in coronary artery anastomosis into senior and junior groups for training and assessment. All trainees received training in coronary artery anastomosis for a defined period. We performed in vivo and in vitro examinations before and after training, respectively. Additionally, we assessed individual surgical performance of surgeons by using performance rating scores, including different aspects of surgical skills rated on a five-point scale. Results: The post-training scores (overall, junior, senior) were significantly higher than the pre-training scores (overall, junior, and senior). We observed no differences in pre-training and post-training scores between the junior and senior groups. Conclusion: Senior surgeons did not had any significant advantages over junior surgeons with respect to coronary artery anastomosis in the absence of training. Junior surgeons achieved the same results as the senior surgeons after training.
Introduction: Allergic rhinitis is a chronic inflammatory disease which affects 1 out of 6 individuals. Perennial allergic rhinitis accounts for 40% of AR cases. Ciclesonide is one of the relatively new intranasal steroid for allergic rhinitis. Objective: The purpose of this study was to evaluate the efficacy and safety of ciclesonide in the treatment of perennial allergic rhinitis. Methods: We searched Pubmed, Scientific Citation Index, Embase, Clinical Trial Registries for randomized controlled trials and Cochrane Central Register of Controlled Trials to find out the randomized controlled Trial comparing ciclesonide with placebo for PAR. Results: Eight studies were included. In comparison with placebo groups, ciclesonide groups significantly decreased Reflective Total Nasal Symptom Score (MD = -0.56; 95% CI -0.72 to 0.39, p < 0.00001) with heterogeneity (p = 0.19, I-2 = 24%), Instantaneous Total Nasal Symptom Score (MD = -0.57; 95% CI -0.75 to -0.39, p < 0.00001) with heterogeneity (p = 0.34, I-2 = 11%). A significant effect for Reflective Nasal Symptom Score Subtotal (MD = -0.15; 95% CI -0.18 to -0.13, p < 0.00001) with heterogeneity (p = 0.12, I-2 = 24%) was also demonstrated. Rhinoconjunctivitis quality of life questionnaire score (RQLQs) (MD = -0.27; 95% CI -0.39 to -0.15, p < 0.00001) with heterogeneity (p = 0.58, I-2 = 0%) in the treatment of ciclesonide was also significantly reduced. In addition, the difference in Treatment-Emergent Adverse Events between the two groups was not significant. Conclusion: Ciclesonide can improve perennial allergic rhinitis without increasing adverse events. Ciclesonide may be another valuable choice for perennial allergic rhinitis in the future. (C) 2018 Associacao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial. Published by Elsevier Editora Ltda.
We previously found that metformin regulates the ion current conducted by the small conductance calcium-activated potassium channels (SK channels) in the atria of rats with type 2 diabetes mellitus (T2DM) as well as the mRNA and protein expression of the SK2 and SK3 subtypes of SK channels. In this study, we hypothesized that the nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4)/p38 mitogen-activated protein kinase (p38MAPK) signaling pathway was involved in the metformin-mediated regulation of SK2 and SK3 expression in the atria of rats with T2DM. We randomly divided Wistar rats into the control group, the untreated T2DM group, the metformin-treated group, the group receiving subcutaneous injections of the nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor diphenyleneiodonium (DPI), and the group receiving tail vein injections of the p38MAPK agonist anisomycin. Real-time polymerase chain reaction, Western blot, and immunohistochemistry were applied to examine the expression levels of SK2, SK3, NOX4, and phospho-p38MAPK (p-p38MAPK) mRNAs and proteins in the atrial tissue of relevant groups. We observed that the expression levels of NOX4 mRNA and protein and p-p38MAPK protein were significantly elevated in the atria of rats with T2DM compared with the control group. In addition, SK2 protein expression was reduced, whereas SK3 protein expression was increased. The 8-week treatment with metformin markedly reduced the expression levels of NOX4 mRNA and protein and p-p38MAPK protein, upregulated the SK2 expression, and downregulated the SK3 expression. Tail vein injection with anisomycin significantly increased the p-p38MAPK expression while further inhibiting the expression of SK2 and enhancing the expression of SK3. Subcutaneous injection with DPI considerably inhibited the expression of NOX4, further enhanced the expression of SK2 and suppressed the expression of SK3. In addition, subcutaneous injection with DPI significantly suppressed the phosphorylation of p38MAPK. In conclusion, the NOX4/p38MAPK signaling pathway mediates the downregulation of SK2 and the upregulation of SK3 in the atria of rats with T2DM. Long-term metformin treatment upregulates SK2 protein expression and downregulates SK3 protein expression by inhibiting the NOX4/p38MAPK signaling pathway.
Background. The outcomes of different repair strategies of an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) in adolescent and adult patients are uncertain. The long-term outcomes of reimplantation and Takeuchi repair were compared in this study. Methods. We conducted a retrospective review of data collected from patients receiving ALCAPA repair at our institute from January 2005 to December 2016. Short- and long-term outcomes of reimplantation and Takeuchi repair were compared. Results. A total of 50 consecutive patients underwent ALCAPA repair, with an average age of 31.6 +/- 15.6 years and 66% women. No significant differences were found in short-term outcomes between the 2 groups. However, at a median of 65.7 months' follow-up, the major adverse cardiovascular event (MACE) (including all-cause death, admission due to heart failure, new-onset acute myocardial infarction, and repeated revascularization) rate of the Takeuchi repair group was significantly lower than that of the reimplantation group (hazard ratio, 0.21; 95% confidence interval, 0.04 to 0.97). Furthermore, the preoperative glucose level was significantly associated with increased MACE rate (hazard ratio, 10.82; 95% confidence interval, 1.20 to 97.54). Left ventricular enddiastolic diameter and ejection fraction significantly improved in both groups. However, mitral valvuloplasty did not predict long-term recovery of left ventricular function. Conclusions. Although short-term outcomes were satisfactory in both groups, a higher MACE rate was observed in reimplantation group than Takeuchi repair group; mitral valvuloplasty was not significantly associated with improved prognosis and left ventricular reverse remodeling. Elevation of preoperative blood glucose level was significantly associated with increasing long-term MACE rate. (C) 2018 by The Society of Thoracic Surgeons
BACKGROUND:The incidence of Ebstein's anomaly is extremely low, and except for the Mayo Clinic, no cardiac center has reported on a sufficient number of patients. The aim of our study was to report the outcomes of Ebstein's anomaly patients treated with tricuspid valvuloplasty (TVP) or tricuspid valve replacement (TVR).METHODS:TVP or TVR was performed in 245 patients from July 2006 to April 2016. We reviewed patients' records and contacted patients via outpatient service and over the telephone.RESULTS:The mean follow-up time was 43.6 ± 32.6 months, and 224 (91.4%) patients underwent follow-up. The mean operative age was 31.2 ± 15.7 years. TVR was performed in 23 patients, and TVP was performed in 201 patients. The 30-day mortality rate was 1.3%, and the overall survival rate was 97.9% at 5 and 10 years. The early mortality rate of the TVP group was lower than that of the TVR group (0.5% vs. 8.7%, P = 0.028), and the overall mortality rate of the TVP group was lower than that of the TVR group, without statistical significance (1.0% vs. 8.7%). After propensity score matching, the rates of mortality and New York Heart Association class ≥ III were lower in the TVP group than those in the TVR group without statistical significance. Seven patients with Type B Wolff-Parkinson-White (WPW) syndrome underwent one-stage surgery, and arrhythmias disappeared. Six patients suffered from episodes of left ventricular outflow tract obstruction (LVOTO) during surgery. Severe LVOTO could be treated with reoperation of the atrialized right ventricle.CONCLUSIONS:Ebstein's anomaly patients treated with TVP or TVR can experience optimal outcomes with midterm follow-up. However, TVP should be the first-choice treatment. Optimal outcomes can be obtained from one-stage operation in patients with Type B WPW syndrome. Severe LVOTO during surgery might be related to improper operation of the atrialized right ventricle.
BACKGROUND:The effects of retaining residual bundles on surgical outcomes has not been observed, so we evaluated the effects of preoperative knee laxity on clinical outcomes after partial anterior cruciate ligament (ACL) reconstruction for partial ACL rupture in this study. PURPOSE:To evaluate the effects of preoperative knee laxity on clinical outcomes after partial anterior cruciate ligament (ACL) reconstruction for partial ACL rupture. METHODS:The data of 47 patients, who had partial ACL rupture and underwent partial ACL reconstruction, were retrospectively analyzed. According to preoperative kneelax arthrometer and pivot shift test, the 47 patients were divided into group A (kneelax arthrometer ≤5mm and pivot shift test 5mm and/or pivot shift test ≥II grade, n=21). The minimum follow-up duration lasted 2 years. The clinical outcomes were evaluated using IKDC (International Knee Documentation Committee) scoring systems, Lysholm knee scoring scale, Tegner activity rating, Lachman test, Pivot shift test and the kneelax arthrometer. RESULTS:The function and stability examinations for the affected knee joint were significantly improved in both groups after partial ACL reconstruction as compared with preoperative ones (all P<0.01). There were no significant differences in the post-operative Lysholm and Tegner scores, Lachman and Pivot shift test results between both groups (all P>0.05). However, there were significant differences between the two groups in terms of the post-operative IKDC scoring system and kneelax arthrometer examination result (all P<0.05). CONCLUSIONS:In the patients with partial ACL rupture, the mechanical strength of the remnant ligament has significant influence on the therapeutic effects of partial reconstruction. The patients with kneelax arthrometer >5mm and/or pivot shift test ≥II grade still have anterior instability in the affected knee after partial reconstruction.