The PIEZO1/miR-155-5p/GDF6/SMAD2/3 signaling axis is involved in inducing the occurrence and progression of osteoarthritis under excessive mechanical stress.

OBJECTIVE: To elucidate the molecular mechanism of overloading-induced osteoarthritis (OA) and to find a novel therapeutic target. METHODS: We utilized human cartilage specimens, mouse chondrocytes, a destabilization of the medial meniscus (DMM) mouse model, and a mouse hindlimb weight-bearing model to validate the role of overloading on chondrocyte senescence and OA development. Then, we observed the effect of PIEZO1-miR-155-5p-GDF6-SMAD2/3 signaling axis on the preservation of joint metabolic homeostasis under overloading in vivo, in vitro and ex vivo by qPCR, Western blot, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, immunofluorescence, SA-ß-gal staining, CCK8 assay, et al. Finally, we verified the therapeutic effects of intra-articular injection of miR-155-5p inhibitor or recombinant GDF6 on the murine overloading-induced OA models. RESULTS: Chondrocytes sensesed the mechanical overloading through PIEZO1 and up-regulated miR-155-5p expression. MiR-155-5p mimics could copy the effects of overloading-induced chondrocyte senescence and OA. Additionally, miR-155-5p could suppress the mRNA expression of Gdf6-Smad2/3 in various tissues within the joint. Overloading could disrupt joint metabolic homeostasis by downregulating the expression of anabolism indicators and upregulating the expression of catabolism indicators in the chondrocytes and synoviocytes, while miR-155-5p inhibition or GDF6 supplementation could exert an antagonistic effect by preserving the joint homeostasis. Finally, in the in vivo overloading models, intra-articular injection of miR-155-5p inhibitor or recombinant GDF6 could significantly mitigate the severity of impending OA and lessened the progression of existing OA. CONCLUSION: GDF6 overexpression or miR-155-5p inhibition could attenuate overloading-induced chondrocyte senescence and OA through the PIEZO1-miR-155-5p-GDF6-SMAD2/3 signaling pathway. Our study provides a new therapeutic target for the treatment of overloading-induced OA.

Systematic Pharmacology and Experimental Validation to Reveal the Alleviation of Astragalus membranaceus Regulating Ferroptosis in Osteoarthritis.

Background: Astragalus membranaceus (AM) shows promise as a therapeutic agent for osteoarthritis (OA), a debilitating condition with high disability rates. OA exacerbation is linked to chondrocyte ferroptosis, yet the precise pharmacological mechanisms of AM remain unclear. Methods: We validated AM's protective efficacy in an anterior cruciate ligament transection (ACLT) mouse model of OA. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database was utilized to identify AM's active components and their targets. FerrDb (a database for regulators and markers of ferroptosis and ferroptosis-disease associations) pinpointed ferroptosis-related targets, while GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGKB), Therapeutic Target Database (TTD), and DrugBank sourced OA-related genes. Molecular docking analysis further validated these targets. Ultimately, the validation of the results was accomplished through in vitro experiments. Results: AM exhibited anabolic effects and suppressed catabolism in OA chondrocytes. Network pharmacology identified 19 common genes, and molecular docking suggested quercetin, an AM constituent, interacts with key proteins like HO-1 and NRF2 to inhibit chondrocyte ferroptosis. In vitro experiments confirmed AM's ability to modulate the NRF2/HO-1 pathway via quercetin, mitigating chondrocyte ferroptosis. Conclusion: This study elucidates how AM regulates chondrocyte ferroptosis, impacting OA progression, providing a theoretical basis and experimental support for AM's scientific application.

Identification of molecular markers for predicting the severity of heart failure after AMI: An Olink precision proteomic study.

BACKGROUND: Acute myocardial infarction (AMI) still has a high incidence of varying degrees of heart failure (HF). The aim of this study is to identify new molecular markers for predicting the severity of HF after AMI. METHODS: We analyzed demographic indicators, past medical history, clinical indicators, major adverse cardiac events (MACEs) and molecular markers in patients with different Killip classifications after AMI. Olink proteomics was used to explore new molecular markers for predicting different severity of HF after AMI. RESULTS: Neutrophil count was the independent risk factors for in-hospital MACEs. Nineteen differentially expressed proteins (DEPs) increased significantly with increasing Killip classification. Five DEPs were also found to have an AUC (95 % CI) value greater than 0.8: GDF-15, NT-pro BNP, TNF-R2, TNF-R1 and TFF3. CONCLUSIONS: Neutrophil count, GDF-15, TNF-R2, TNF-R1 and TFF3 were closely related to the Killip classification of HF after AMI, which suggests that the inflammatory response plays an important role in the severity of HF after AMI and that regulating inflammation might become a new target for controlling HF.

Expanding from unilateral to bilateral: A robust deep learning-based approach for predicting radiographic osteoarthritis progression.

OBJECTIVE: To develop and validate a deep learning (DL) model for predicting osteoarthritis (OA) progression based on bilateral knee joint views. METHODS: In this retrospective study, knee joints from bilateral posteroanterior knee radiographs of participants in the Osteoarthritis Initiative were analyzed. At baseline, participants were divided into testing set 1 and development set according to the different enrolled sites. The development set was further divided into a training set and a validation set in an 8:2 ratio for model development. At 48-month follow-up, eligible patients were formed testing set 2. The Bilateral Knee Neural Network (BikNet) was developed using bilateral views, with the knee to be predicted as the main view and the contralateral knee as the auxiliary view. DenseNet and ResNext were also trained and compared as the unilateral model. Two reader tests were conducted to evaluate the model's value in predicting incident OA. RESULTS: Totally 3583 participants were evaluated. The BikNet we proposed outperformed ResNext and DenseNet (all area under the curve [AUC] < 0.71, P < 0.001) with AUC values of 0.761 and 0.745 in testing sets 1 and 2, respectively. With assistance of the BikNet increased clinicians' sensitivity (from 28.1-63.2% to 42.1-68.4%) and specificity (from 57.4-83.4% to 64.1-87.5%) of incident OA prediction and improved inter-observer reliability. CONCLUSION: The DL model, constructed based on bilateral knee views, holds promise for enhancing the assessment of OA and demonstrates greater robustness during subsequent follow-up evaluations as compared with unilateral models. BikNet represents a potential tool or imaging biomarker for predicting OA progression.

The association of psychological stress with metabolic syndrome and its components: cross-sectional and bidirectional two-sample Mendelian randomization analyses.

Background: Metabolic syndrome (MetS) is a group of co-occurring conditions that increase the risk of cardiovascular disease, which include the conditions of hypertension, overweight or obesity, hyperglycemia, and dyslipidemia. Psychological stress is gradually being taken seriously, stemming from the imbalance between environmental demands and individual perceptions. However, the potential causal relationship between psychological stress and MetS remains unclear. Method: We conducted cross-sectional and bidirectional Mendelian randomization (MR) analyses to clarify the potential causal relationship of psychological stress with MetS and its components. Multivariable logistic regression models were used to adjust for potential confounders in the cross-sectional study of the Chinese population, including 4,933 individuals (70.1% men; mean age, 46.13 ± 8.25). Stratified analyses of sexual characteristics were also performed. Bidirectional MR analyses were further carried out to verify causality based on summary-level genome-wide association studies in the European population, using the main analysis of the inverse variance-weighted method. Results: We found that higher psychological stress levels were cross-sectionally associated with an increased risk of hypertension in men (odds ratio (OR), 1.341; 95% confidence interval (CI), 1.023-1.758; p = 0.034); moreover, higher levels of hypertension were cross-sectionally associated with an increased risk of psychological stress in men and the total population (men: OR, 1.545 (95% CI, 1.113-2.145); p = 0.009; total population: OR, 1.327 (95% CI, 1.025-1.718); p = 0.032). Genetically predicted hypertension was causally associated with a higher risk of psychological stress in the inverse-variance weighted MR model (OR, 2.386 (95% CI, 1.209-4.710); p = 0.012). However, there was no association between psychological stress and MetS or the other three risk factors (overweight or obesity, hyperglycemia, and dyslipidemia) in cross-sectional and MR analyses. Conclusion: Although we did not observe an association between psychological stress and MetS, we found associations between psychological stress and hypertension both in cross-sectional and MR studies, which may have implications for targeting hypertension-related factors in interventions to improve mental and metabolic health. Further study is needed to confirm our findings.

Uncemented Tibial Fixation Has Comparable Prognostic Outcomes and Safety Versus Cemented Fixation in Cruciate-Retaining Total Knee Arthroplasty: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Cemented and uncemented fixation are the primary methods of tibial prosthesis fixation in total knee arthroplasty. However, the optimal fixation method remains controversial. This article explored whether uncemented tibial fixation has better clinical and radiological outcomes, fewer complications, and revision rates compared to cemented tibial fixation. METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases up to September 2022 to identify randomized controlled trials (RCTs) that compared uncemented total knee arthroplasty (TKA) and cemented TKA. The outcome assessment consisted of clinical and radiological outcomes, complications (aseptic loosening, infection, and thrombosis), and revision rate. Subgroup analysis was used to explore the effects of different fixation methods on knee scores in younger patients. RESULTS: Nine RCTs were finally analyzed with 686 uncemented knees and 678 cemented knees. The mean follow-up time was 12.6 years. The pooled data revealed significant advantages of uncemented fixations over cemented fixations in terms of the Knee Society Knee Score (KSKS) (p = 0.01) and the Knee Society Score-Pain (KSS-Pain) (p = 0.02). Cemented fixations showed significant advantages in maximum total point motion (MTPM) (p < 0.0001). There was no significant difference between uncemented fixation and cemented fixation regarding functional outcomes, range of motion, complications, and revision rates. When comparing among young people (<65 years), the differences in KSKS became statistically insignificant. No significant difference was shown in aseptic loosening and the revision rate among young patients. CONCLUSIONS: The current evidence shows better knee score, less pain, comparable complications and revision rates for uncemented tibial prosthesis fixation, compared to cemented, in cruciate-retaining total knee arthroplasty.

A case of diffuse large B-cell lymphoma with interstitial pneumonia.

This report involves a 54-year-old female patient diagnosed with diffuse large B-cell lymphoma who developed interstitial pneumonia (IP) during treatment. The patient presented to the ward with enlarged lymph nodes in the neck and was treated with the standard regimen, which included rituximab, cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (R-CDOP regimen). After 3 cycles, the treatment was assessed as effective. However, following the 4th cycle, the patient experience shortness of breath after physical activity. A repeat lung computer tomography indicated IP, which completely recovered after receiving "full coverage" treatment. Subsequently, the patient underwent 2 cycles of cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (CDOP), followed by local radiotherapy. Currently, the patient is now being followed up with regular reviews.

Effects of ankle-brachial index and brachial-ankle pulse wave velocity on all-cause mortality in a community-based elderly population.

Background: Ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are both important indicators of arterial stiffness and vascular injury. At present, most studies on the relationship between ABI and baPWV and all-cause mortality in community-based elderly are analyzing ABI or baPWV alone, and will focus on a single special population such as diabetes and stroke. The purpose of this study was to evaluate the relationship between ABI and baPWV in a Chinese community-based elderly population, and to analyze their impact on all-cause mortality in a community-based population through a follow-up of nearly 10 years. Methods: Participants were residents of the Wanshou Road community in Beijing, China. A total of 2,162 people in the community were included, with an average age of 71.48 years. During a mean follow-up period of 9.87 years, 1,826 subjects completed follow-up. Kaplan-Meier survival analysis and different Cox regression models were used to verify the association of ABI and baPWV with all-cause mortality. The selected subjects were divided into two groups according to ABI and baPWV, and ABI was divided into two groups with 0.90 as the cut-off point (group 1: 0.9 < ABI ≤ 1.3; group 2: ABI ≤ 0.9); according to the level of baPWV, they were divided into three groups (Tertile 1: baPWV <1761.5 cm/s; Tertile 2: 1761.5 ≤ baPWV <2121.5 cm/s; Tertile 3: baPWV ≥2121.5 cm/s). Results: 1,826 people were included in the statistical analysis, and the total mortality rate was 181.3/1000. The 10-year all-cause mortality rate of the abnormal ABI group (group 2) was 44.7%, and that of the normal ABI group (group 1) was 17.0%; The 10-year all-cause mortality rates from low to high in the baPWV tertile were 10.0%, 18.7%, and 26.4%. In the Cox proportional hazards model, after adjusting for possible confounders, the effect of baPWV on all-cause mortality was significant, with the 3rd tertile having a 1.647-fold higher risk of all-cause mortality than the 1st tertile (P = 0.014 ). Conclusions: ABI and baPWV are risk factors affecting all-cause mortality in the elderly community population, and baPWV is an independent predictor of all-cause mortality in the elderly community population.

Arthroscopic Direct Anterior-to-Posterior Suture Suspension Fixation for the Treatment of Posterior Cruciate Ligament Tibial Avulsion Fracture.

OBJECTIVES: A posterior cruciate ligament (PCL) avulsion fracture of the tibial attachment site is a specific type of PCL injury that is difficult and unpleasant to manage. The objective of this study is to report the preliminary results of a newly developed technique: arthroscopic endobutton-suture fixation using a single tibial tunnel. METHODS: From January 2016 to January 2018, 120 patients with PCL avulsion fracture who met our criteria were recruited. Sixty cases were treated by arthroscopic direct anterior-to-posterior suture suspension fixation (endobutton-suture group), and 60 cases were treated by arthroscopic screw-suture fixation (screw-suture group). All radiographic studies were recorded. The curative effect was evaluated by the range of motion (ROM), KT-2000, International Knee Documentation Committee (IKDC) scores, Tegner activity scale, and Lysholm scoring system. For statistical analysis the Student t-test was used. RESULTS: The average follow-up duration was 24 months. Findings and difficulties in surgery are the following. The lax anterior cruciate ligament is one of the diagnostic criteria. The anatomic location of PCL avulsion fractures is deep and surrounded by nerves and vessels; thus, operating through this region is difficult. After each tunnel drilling, the debris at the edge of opening needs to be cleaned to avoid obscuring the operator's vision or wearing the sutures. In endobutton-suture group, ROM improved from 0° preoperatively to 140.0° ± 5.6° at the last follow-up (P < 0.001). The postoperative KT-2000 arthrometric data at 90 N were available for all patients. The IKDC score was 23.6 ± 2.6 and 91.4 ± 4.1 pre- and postoperatively, respectively. The Tegner score improved from 1.2 ± 0.6 to 7.3 ± 2.3 (p < 0.001). The median Lysholm knee score increased from 40.4 ± 5.2 preoperatively to 90.1 ± 10.1 postoperatively (p < 0.001). The operative time was shorter in the endobutton-suture group (p < 0.001). The Lysholm knee score in the endobutton-suture group was lower than that in the endobutton-suture group (3.1 ± 1.2 vs. 4.2 ± 1.8, p < 0.01). No significant complications were noted in the study. CONCLUSIONS: The arthroscopic direct anterior-to-posterior suture suspension fixation is a simple and reliable method that not only provides better clinical outcomes, but also fixes avulsion fragments of any size.

Qi-Regulating and Blood Circulation-Promoting Therapy Improves Health Status of Stable Angina Pectoris Patients with Depressive Symptoms.

Depressive symptoms have been found to be highly prevalent among patients with coronary heart disease (CHD) and seriously affect the patients' quality of life. However, most psychotropic drugs have warnings about potential side effects. Accordingly, safer effective alternatives are urgently demanded. Angina pectoris of CHD is considered as "chest stuffiness and heartache syndrome" in traditional Chinese medicine, with the major syndrome type named Qi stagnation and blood stasis. Qi-regulating and blood circulation-promoting therapy has increasingly shown unique advantages in CHD patients. This study investigated the efficacy of Xuefu Zhuyu decoction, a representative prescription of Qi-regulating and blood circulation-promoting therapy, on angina pectoris patients with depressive symptoms. Depressive symptoms were stratified at baseline in 30 patients with stable angina pectoris who participated in both baseline and 12-week follow-up studies. After performing a stratified analysis, the angina pectoris-specific health status and traditional Chinese medicine "chest stuffiness and heartache syndrome" were evaluated by self-reports using the associated questionnaire scales, respectively. We measured serum concentrations of serotonin, brain-derived neurotrophic factor, and ATP, which are associated with the development of depression. We found that the Xuefu Zhuyu granule significantly improved the angina pectoris-specific health status in patients after 12 weeks of treatment; specifically, it had a better curative effect on patients with depressive symptoms. Xuefu Zhuyu granule also significantly improved the chest stuffiness and heartache syndrome in patients with depressive symptoms (efficacy index is 61.24%, P < 0.05 versus baseline). Interestingly, Xuefu Zhuyu granule has been found to be more susceptible to improving ATP levels in patients with depressive symptoms, indicating that the improvement in serum ATP levels might account for the better efficacy of Xuefu Zhuyu granule in patients with depressive symptoms. Our data provide prospective evidence that Xuefu Zhuyu granule improves angina pectoris-specific health status through regulating Qi and promoting blood circulation. This trial is registered with ChiCTR-IOR-15006989.

Effects of Xuefu Zhuyu Granules on Patients with Stable Coronary Heart Disease: A Double-Blind, Randomized, and Placebo-Controlled Study.

Despite advances in the drug treatment strategy for stable coronary heart disease (CHD), the mortality of CHD continues to rise. New or adjuvant treatments would be desirable for CHD. Xuefu Zhuyu granules are derived from the formula of traditional Chinese medicine. To determine whether Xuefu Zhuyu granules might have adjuvant effects on stable CHD, we conducted a controlled clinical trial. Patients with stable CHD were enrolled and randomly assigned to receive Xuefu Zhuyu granules or placebo for 12 weeks in addition to their standard medications for the treatment of CHD. The primary endpoints comprise the Canadian Cardiovascular Society Angina Grading Scale (CCS class), echocardiographic measures, Seattle Angina Questionnaire (SAQ), and coronary artery CT. The secondary endpoints included the parameters of nailfold capillary measurement and cutaneous blood perfusion (CBP). After 12 weeks of follow-up, there was a great improvement of the Canadian Cardiovascular Society Angina Grading Scale (CCS class) in the Xuefu Zhuyu group compared with the placebo group (p < 0.01). Also, a decrease was found in the percentage of patients with CCS class II in the Xuefu Zhuyu group between follow-up at 12 weeks and baseline (p < 0.01). We observed a significant increase in SAQ scores of physical limitation (p < 0.01) and treatment satisfaction (p < 0.05) in patients receiving Xuefu Zhuyu treatment at 12 weeks in comparison with those at baseline, but not in placebo treatment (p > 0.05). Amelioration in coronary artery stenosis in the Xuefu Zhuyu group was noted (p < 0.05). Xuefu Zhuyu granule treatment led to great improvements in cutaneous blood perfusion at follow-up of 12 weeks compared with placebo (p < 0.05). These findings suggest that on a background of standard medications, Xuefu Zhuyu granules have the ability to further improve the prognosis of patients with stable CHD.

Attenuation of the upregulation of NF­κB and AP­1 DNA­binding activities induced by tunicamycin or hypoxia/reoxygenation in neonatal rat cardiomyocytes by SERCA2a overexpression.

The present study aimed to investigate the effects of the overexpression of sarco/endoplasmic reticulum Ca2+­ATPase (SERCA2a) on endoplasmic reticulum (ER) stress (ERS)­associated inflammation in neonatal rat cardiomyocytes (NRCMs) induced by tunicamycin (TM) or hypoxia/reoxygenation (H/R). The optimal multiplicity of infection (MOI) was 2 pfu/cell. Neonatal Sprague­Dawley rat cardiomyocytes cultured in vitro were infected with adenoviral vectors carrying SERCA2a or enhanced green fluorescent protein genes, the latter used as a control. At 48 h following gene transfer, the NRCMs were treated with TM (10 µg/ml) or subjected to H/R to induce ERS. The results of electrophoretic mobility shift assay (EMSA) revealed that overexpression of SERCA2a attenuated the upregulation of nuclear factor (NF)­κB and activator protein­1 (AP­1) DNA­binding activities induced by TM or H/R. Western blot analysis and semi­quantitative RT­PCR revealed that the overexpression of SERCA2a attenuated the activation of the inositol­requiring 1α (IRE1α) signaling pathway and ERS­associated apoptosis induced by TM. The overexpression of SERCA2a also decreased the level of phospho­p65 (Ser536) in the nucleus, as assessed by western blot analysis. However, the overexpression of SERCA2a induced the further nuclear translocation of NF­κB p65 and higher levels of tumor necrosis factor (TNF)­α transcripts in the NRCMs, indicating the occurrence of the ER overload response (EOR). Therefore, the overexpression of SERCA2a has a 'double­edged sword' effect on ERS­associated inflammation. On the one hand, it attenuates ERS and the activation of the IRE1α signaling pathway induced by TM, resulting in the attenuation of the upregulation of NF­κB and AP­1 DNA­binding activities in the nucleus, and on the other hand, it induces EOR, leading to the further nuclear translocation of NF­κB and the transcription of TNF­α. The preceding EOR may precondition the NRCMs against subsequent ERS induced by TM. Further studies using adult rat cardiomyocytes are required to prevent the interference of EOR. The findings of the present study may enhance the current understanding of the role of SERCA2a in cardiomyocytes.

Efficacy and Safety Evaluation of Taohong Siwu Decoction () for Patients with Angina Pectoris: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To assess the efficacy and safety of Taohong Siwu Decoction (, TSD), a Chinese herbal compound prescription, in patients with angina pectoris (AP). METHODS: Randomized clinical trials (RCTs) comparing TSD plus conventional treatment (CT) with CT plus placebo or CT only in the patients with AP were searched in PubMed, Cochrane Library, Excerpta Medica Database, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Database, Chinese Scientific Journal Database, Chinese Clinical Trial Registry and International Clinical Trial Registry from their inception to March 2017. The primary outcomes include a composite event of death, acute myocardial infarction (AMI), and target vessel revascularization. The secondary outcomes include angina symptom, electrocardiogram (ECG) improvement and serum high-sensitivity C-reactive protein (hs-CRP), endothelin-1 (ET-1), triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. The methodological quality of included studies and extracted available data were assessed. RevMan 5.3 software was used to conduct statistical analysis. The relative risk (RR) and standardized mean difference (SMD) with 95% confidence interval (CI) was calculated. A funnel plot was used to evaluate the publication bias. RESULTS: Among 204 studies identified in the literature search, 12 trials including 959 patients with AP met the inclusion criteria. No studies reported the primary outcome including death, AMI and target vessel revascularization. TSD combined with CT showed significant improvement in relieving angina symptom [RR=3.70, 95% CI (2.42, 5.67)] and ECG [RR=3.20, 95% CI (2.20, 4.65)] compared with CT alone. TSD combined with CT reduced the serum hs-CRP, TG, TC and LDL-C levels compared with CT alone. No serious adverse events were reported in TSD combined with CT. CONCLUSIONS: TSD combined with CT has a potential benefit on relieving AP without significant adverse events. However, the efficacy on the cardiovascular events needs to be assessed by more rigorously-designed, largescale, and multi-center RCTs in future.

Endoscopic reconstruction for chronic Achilles tendon ruptures using a hamstring tendon autograft.

BACKGROUND: To determine the safety and efficacy of endoscopic reconstruction of chronic Achilles tendon ruptures using a hamstring tendon autograft at mid-term follow-up. METHODS: We reviewed the medical records of patients with chronic Achilles tendon rupture treated surgically by endoscopic reconstruction using a hamstring tendon autograft at our institution between March 2010 and October 2015. Radiologic outcomes were assessed using pre- and postoperative magnetic resonance imaging (MRI). Functional outcomes were evaluated with the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, the Plantar Flexion Strength (PFS), the Victorian Institute of Sport Assessment-Achilles (VISA-A) scale, the Visual Analogue Scale (VAS) pain score, and the Arner-Lindholm standard. All patients achieved primary healing with no lengthening of the Achilles tendon, skin necrosis, infection, deep vein thrombosis or other complications. RESULTS: Mean follow-up period was 15 ± 3 months (range, 12-18 months). There was no Achilles tendon re-rupture. MRI examination revealed that Achilles tendon continuity was restored. Patients' mean AOFAS, PFS, and VISA-A scores were significantly higher and mean VAS pain score was significantly lower after surgery compared to before (P < 0.05). According to Arner-Lindholm standards, there were twenty (76.9%) excellent, six (23.1%) good, and zero bad outcomes. CONCLUSION: Endoscopic reconstruction utilizing a hamstring tendon autograft is a safe and efficacious option for repair of chronic Achilles tendon ruptures. Studies with larger sample sizes and a longer follow-up are required to confirm the advantage of this technique compared to open surgery.

Traditional Chinese Medicines alleviated myocardial ischemia by regulating Qi and promoting blood circulation.

OBJECTIVE: To investigate the efficacy of Chinese medicines on Qi stagnation and blood stasis in rats with myocardial ischemia. METHODS: Fifty male Wistar rats were randomly divided into five groups (n = 10) as follows: (a) sham operation (Sham), (b) myocardial ischemia (Model), (c) treatment that regulates Qi (Qi), (d) treatment that promotes blood circulation (Blood), (e) treatment that both regulates Qi and promotes blood circulation (QB). The rat model was established via activities restriction for 6 h followed by tail clamp stimulation for 5 mins every day for 7 d and occlusion left coronary anterior descending artery. Afterwards rats were treated with medicines that regulate Qi and/or promote blood circulation via gavage for 14 d. Behavioral parameters were evaluated using open field and elevated plus-maze tests. The tongue color and sublingual vein were visually examined. Blood flow perfusion of tongue and auricle were detected using PIM Ⅱ. The mesenteric microcirculation was examined via capillaroscopy, and hemodynamics was assessed using a polygraph system. Serum homocysteine (Hcy), creatine kinase isoenzyme (CKMB) levels and endothelin-1 (ET-1) were measured. Hematoxylin and eosin staining and transmission electron microscopy were employed to detect the myocardial morphology and ultrastructure, respectively. RESULTS: Compared with findings in Sham group, rats in model group had coarse hair, dark mucosa of the lips and claw, low activity, and increased anxiety. Compared with findings in Model group, rats in the three treatment groups exhibited a lighter tongue color without an extended and varicose sublingual vein. There were significant increases of auricle blood flow perfusion in the Qi group and tongue bottom blood flow perfusion in the QB group. Compared with findings in Model rats, rats in Blood group exhibited improved mesenteric microcirculation associated with increased mesenteric blood flow and a larger arteriole diameter. Moreover, compared with findings in Model rats, Qi and QB rats exhibited increased left ventricular ± dp/dtmax, decreased serum CKMB, Hcy, ET-1 levels, and reduced myocardial ultrastructural damage. CONCLUSION: Myocardial ischemia damage was suppressed by Traditional Chinese Medicines that regulate Qi and promote blood circulation.

A modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction: medium-term clinical and radiologic results comparable with open reconstruction.

BACKGROUND: The aim of this study was to compare clinical and radiologic outcomes of a modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction with traditional open reconstruction. METHODS: From January 2012 and March 2016, 60 eligible patients with chronic lateral ankle instability (CLAI) received all arthroscopic remnant-preserving reconstruction or open reconstruction of the anterior talofibular ligament and calcaneofibular ligament using semitendinosus autograft. They were divided into the arthroscopic group (n = 28) and the open group (n = 32). The American Orthopaedic Foot and Ankle Society (AOFAS),visual analog scale (VAS), and Karlsson scores and ankle range of motion (ROM) were used to evaluate clinical outcomes pre-operatively and at six and 12 months and the final follow-up of at least 24 months post-operatively, with SF-36 physical component summary (PCS) and mental component summary (MCS) scores evaluated for quality of life, and the anterior talar translation and talar tilt measurements for radiologic outcomes. RESULTS: There was no difference in pre-operative demographics between two groups (P > 0.05). At the final follow-up, the AOFAS, VAS, Karlsson, SF-36 PCS, and MCS scores improved significantly in both groups (P < 0.05). However, no significant difference was found in AOFAS (91.9 ± 6.8 vs 91.1 ± 5.5), VAS (2.7 ± 1.7 vs 2.5 ± 1.6), Karlsson (95.3 ± 6.7 vs 94.8 ± 6.5), SF-36 PCS (53.2 ± 6.1 vs 52.9 ± 5.7), and MCS scores (55.7 ± 5.8 vs 54.2 ± 5.4) between the two groups (P > 0.05). There was no significant difference in post-operative operated/non-operated ankle ROM between two groups (P > 0.05). No significant difference was observed in talar tilt angle (7.6 ± 4.1° vs 6.8 ± 3.6°) and anterior talar translation (5.8 ± 1.7 mm vs 5.7 ± 1.5 mm) between the two groups at the final follow-up (P > 0.05), although these two variables improved significantly in both groups (P < 0.05). No severe complications were encountered in both groups during the follow-up period. CONCLUSIONS: The modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction could produce excellent clinical and radiologic outcomes comparable with open reconstruction.

[Clinical analysis of autogenous tendon reconstruction under total arthroscopy in treatment of chronic Achilles tendon rupture].

OBJECTIVE: To investigate the effectiveness of autogenous tendon reconstruction under total arthroscopy in the treatment of chronic Achilles tendon rupture. METHODS: Between June 2015 and June 2018, 16 patients with chronic Achilles tendon ruptures were treated by autogenous tendon reconstruction under total arthroscopy. Of the 16 patients, 11 were males and 5 were females. Their mean age was 40.7 years (range, 21-55 years). The disease duration was 14-20 months (mean, 16.4 months). Preoperative American Orthopaedic Foot and Ankle Society (AOFAS) score was 41.2±2.2 and the pain visual analogue scale (VAS) score was 7.9±1.2. MRI and B-ultrasonography examinations showed that the Achilles tendon was not continuous. The length of Achilles tendon defect was 5.0-10.3 cm, with an average of 5.8 cm. The rupture of the Achilles tendon happened on top of the insertion of the tendon in 4 cases and at the tendon-muscle belly connection in 12 cases. The operation time, intraoperative blood loss, hospital stay, and related complications were recorded. The AOFAS score and VAS score were used to evaluate the improvement of ankle joint function and pain. RESULTS: The average operation time was 77.2 minutes (range, 60-90 minutes). The average intraoperative blood loss was 20.5 mL (range, 15-30 mL). The average hospital stay was 7.2 days (range, 5-10 days). All incisions healed by first intention. There was no skin necrosis, infection, or deep vein thrombosis. All the patients were followed up 8-18 months, with an average of 12 months; and 10 cases were followed up more than 12 months. During the follow-up, there was no Achilles tendon re-rupture, and the symptoms of pain and heel lifting failure significantly improved. MRI reexamination showed that the continuity of Achilles tendon recovered. At 1, 3, 6, and 12 months postoperatively, AOFAS scores significantly improved and VAS scores significantly reduced, except for 1 month postoperatively, the scores at other time points were superior to that before operation, the differences were significant ( P<0.05). CONCLUSION: Autogenous tendon reconstruction under total arthroscopy in the treatment of chronic Achilles tendon rupture has the advantages of small trauma, rapid functional recovery, and satisfactory surgical efficacy.

Non-Targeted Metabolomic Profiling of Coronary Heart Disease Patients With Taohong Siwu Decoction Treatment.

Traditional Chinese medicine is one of the complementary and alternative therapies to improve the prognosis of coronary heart disease (CHD). Taohong Siwu Decoction (THSWD), a classical traditional Chinese medication that promotes blood circulation, is clinically beneficial in CHD. However, the underlying mechanism of THSWD is still unclear. To comprehensively understand the material foundation of the "blood", it is significantly important to study the differential metabolites involved in the treatment of CHD with Chinese medicinal herb promoting blood circulation in TCM theory. Hence, this study investigated the metabolic profiles of the serum in CHD patients to determine the differential metabolites between the THSWD group and the placebo group. Eleven CHD patients were recruited and divided into two groups randomly and double-blindly. Serum samples were determined by performing non-targeted ultra-performance liquid chromatography with tandem mass spectrometry-based metabolomics. Pearson's correlation analysis was used to assess the association between identified metabolites and clinical serum indexes of CHD. Based on the result, a total of 513 metabolites were found in the serum of CHD patients, of which 27, involved in 29 metabolic pathways, were significantly different between the two groups. Among the differential metabolites, THSWD upregulated succinylcarnitine in fatty acid metabolism and 5'-methylthioadenosine in cysteine and methionine metabolism compared with the placebo group. However, THSWD downregulated pelargonic acid, involved in FA metabolism; succinate, involved in the tricarboxylic acid cycle; gluconic acid, gluconolactone, and d-glucose, involved in pentose phosphate pathway; glycerophosphocholine, involved in glycerophospholipid metabolism; 8,9-dihydroxyeicosatrienoic acid (8,9-DiHETrE), l-lysine, N-acetyl-l-aspartic acid, N-alpha-acetyl-l-asparagine, hippurate, indoxyl sulfate, and 3-ureidopropionate involved in amino acid metabolism compared with the placebo group. Moreover, succinylcarnitine, pelargonic acid, succinate, d-glucose, gluconic acid, l-lysine, N-alpha-acetyl-l-asparagine, 5'-methylthioadenosine, indoxyl sulfate, 8,9-DiHETrE, and 3-ureidopropionate were associated with total cholesterol or low-density lipoprotein. Succinylcarnitine, pelargonic acid, gluconolactone, N-acetyl-l-aspartic acid, N-alpha-acetyl-l-asparagine, hippurate, and 5'-methylthioadenosine were associated with activated partial thromboplastin time. Our findings indicated that glycerophosphocholine, 8,9-DiHETrE, 5'-methylthioadenosine, hippurate, indoxyl sulfate, and 3-ureidopropionate might constitute the partial material foundation of the "blood" in CHD patients treated with THSWD.

Surgery-induced cognitive dysfunction is alleviated through triggering receptor expressed on myeloid cells 2.

Neuroinflammation plays a key role in perioperative neurocognitive disorders (PND). Increased evidences indicate that triggering receptor expressed on myeloid cells 2 (TREM2) can mitigate inflammatory response in the brain, and the aim of this study is to investigate whether TREM2 is involved in surgery-induced cognitive dysfunction in adult mice. We used adult C57BL/6 mice subjected to intramedullary fixation surgery, and found that surgery did not impair the motor ability of mice, but worsened the learning and memory function, and reduced the expression of TREM2. Meanwhile, up-regulated TREM2 expression in the brain of mice, induced by selective TREM2 agonist HSP60, significantly improved the learning and memory, alleviated the neuroinflammation, and decreased the neuronal cell apoptosis in mice. Meanwhile, TREM2-siRNA abolished the increased expression of TREM2 induced by HSP60, and reversed all the HSP60-induced beneficial effects. Therefore, our study indicated that up-regulation of TREM2 alleviated neuroinflammation and improved learning and memory function after surgery in mice.

The establishment of rat model in myocardial ischemia with psychological stress.

BACKGROUND: Psychological stress can provoke and aggravate myocardial ischemia, and this stress can even trigger acute coronary syndromes or sudden cardiac death. Therefore, for the first time, this study aimed to investigate the method for establishing a rat model of myocardial ischemia with psychological stress and its evaluation. METHODS: Forty male Wistar rats were randomly divided into the sham (S, n=10), myocardial infarct (MI, n=10), psychological stress (MODEL, n=10), and myocardial infarct with psychological stress (MI + MODEL, n=10) groups. The rat model of psychological stress was established by measuring the data from activity restriction for 6 hours and followed by tail clamp stimulation for 5 minutes every day for 14 days. The rat model of the myocardial infarct with psychological stress was established by occluding the left coronary anterior descending artery in the MODEL rats. The body weight of rats was measured daily, the behavior parameters were evaluated via open-field test and elevated plus-maze, tongue color and sublingual vein were observed, rats' acral blood flow perfusion was detected by PIM II (Perfusion Imager II), mesenteric microcirculation was measured by capillaroscopy, and hemodynamics was measured by a polygraph system. An automatic biochemical analyzer determined the content of serum cTnT (cardiac troponin T), Hcy (homocysteine), and activity of LDH (lactate dehydrogenase). Myocardial infarct size was measured with TTC (triphenyhetrazolium chloride) staining. RESULTS: We found that rats in the psychological stress (MODEL) group were characterized by coarse hair, dark mucosa of the lips and claw, low spirit, decreased body weight, and increased anxiety. Compared with rats in the sham group, rats in the MODEL + MI group showed decreased mesenteric blood flow, narrowed arteriole and venule diameter, reduced acral blood flow perfusion, and LV ±dp/dtmax (the maximal rate of the increased and decrease of left ventricular pressure), as well as increased serum content of cTnT, Hcy, and LDH activity. Compared with the MI group, rats in the MODEL + MI group showed deteriorated microcirculation dysfunction manifested as a dark tongue color of deep purple, prominently extended and varicose sublingual vein, and aggravated myocardial damage in the form of increased infarct size and LDH leakage. CONCLUSIONS: In conclusion, the rat model of myocardial ischemia with psychological stress was successfully established, and manifested as aggravating behavioral disorder, mesenteric microcirculation and left ventricular dysfunction, and myocardial damage.